Importance of placebo effect in cough clinical trials.

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Eccles, Ron

2010-01-01

Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed.

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

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Li Li

2010-05-01

Full Text Available Abstract Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p ® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0% subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601

Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

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Ito Mikako

2011-10-01

Full Text Available Abstract Background Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. Methods We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD, four patients with polymyositis/dermatomyositis (PM/DM, and five patients with mitochondrial myopathies (MM, and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. Results In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3 in PM/DM, and serum triglycerides in PM/DM. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin

Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study.

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Safarinejad, Mohammad Reza

2005-01-01

To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P Urtica dioica group (from 40.1 cc initially to 36.3 cc; P Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.

Immediate effects of kinesiotaping on quadriceps muscle strength: a single-blind, placebo-controlled crossover trial.

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Vercelli, Stefano; Sartorio, Francesco; Foti, Calogero; Colletto, Lorenzo; Virton, Domenico; Ronconi, Gianpaolo; Ferriero, Giorgio

2012-07-01

To investigate the immediate effects on maximal muscle strength of kinesiotaping (KT) applied to the dominant quadriceps of healthy subjects. Single-blind, placebo-controlled crossover trial. "Salvatore Maugeri" Foundation. With ethical approval and informed consent, a convenience sample of 36 healthy volunteers were recruited. Two subjects did not complete the sessions and were excluded from the analysis. Subjects were tested across 3 different sessions, randomly receiving 2 experimental KT conditions applied with the aim of enhancing and inhibiting muscle strength and a sham KT application. Quadriceps muscle strength was measured by means of an isokinetic maximal test performed at 60 and 180 degrees per second. Two secondary outcome measures were performed: the single-leg triple hop for distance to measure limb performance and the Global Rating of Change Scale (GRCS) to calculate agreement between KT application and subjective perception of strength. Compared with baseline, none of the 3 taping conditions showed a significant change in muscle strength and performance (all P > 0.05). Effect size was very low under all conditions (≤0.08). Very few subjects showed an individual change greater than the minimal detectable change. Global Rating of Change Scale scores demonstrated low to moderate agreement with the type of KT applied, but some placebo effects were reported independently of condition. Our findings indicated no significant effect in the maximal quadriceps strength immediately after the application of inhibition, facilitation, or sham KT. These results do not support the use of KT applied in this way to change maximal muscle strength in healthy people.

A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study.

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Ridha, Basil H; Crutch, Sebastian; Cutler, Dawn; Frost, Christopher; Knight, William; Barker, Suzie; Epie, Norah; Warrington, Elizabeth K; Kukkastenvehmas, Riitta; Douglas, Jane; Rossor, Martin N

2018-05-01

The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease. A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p effect on MMSE. Therefore, the analysis of treatment effect on MMSE was restricted to the first 12-week period. Treatment effect at 6 weeks was statistically significant (difference = 2.5 in favour of donepezil, 95% CI 0.1 to 5.0, p effect at 12 weeks was close, but not statistically significant (difference = 2.0 in favour of donepezil, 95% CI -0.1 to 4.5, p > 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and were the cause of study discontinuation in one

The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial.

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Pakdaman, Michael N; Udani, Jay K; Molina, Jhanna Pamela; Shahani, Michael

2016-05-20

Lactose intolerance is a form of lactose maldigestion where individuals experience symptoms such as diarrhea, abdominal cramping, flatulence, vomiting and bowel sounds following lactose consumption. Lactobacillus acidophilus is a species of bacteria known for its sugar fermenting properties. Preclinical studies have found that Lactobacillus acidophilus supplementation may assist in breaking down lactose; however, no human clinical trials exist evaluating its efficacy in alleviating symptoms related to lactose intolerance. The aim of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of a proprietary strain of Lactobacillus acidophilus on relieving discomfort related to lactose intolerance. The study enrolled healthy volunteers between 18 and 75 years of age who complained of lactose intolerance. Screening visits included a lactose challenge visit to confirm eligibility based on a score of 10 or higher on subjective assessment of the following symptoms after lactose challenge: diarrhea, abdominal cramping, vomiting, audible bowel sounds, flatulence, and overall symptoms. Qualified subjects participated in a 2-arm crossover design, with each arm consisting of 4 weeks of intervention of either active or placebo product, with a 2-week washout period during crossover. The study product consisted of the DDS-1 strain of Lactobacillus acidophilus (Nebraska Cultures, Walnut Creek, California). The placebo was formulated from maltodextrin. Study participants were instructed to take the product once daily for 4 weeks. Data collected included subjective symptom scores related to lactose intolerance. Longitudinal comparison between the DDS-1 group and placebo group demonstrated statistically significant reductions in abdominal symptom scores during the 6-h Lactose Challenge at week 4 for diarrhea (p = 0.033), abdominal cramping (p = 0.012), vomiting (p = 0.0002), and overall symptom score (p = 0.037). No adverse

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

OpenAIRE

Quintana, D S; Westlye, L T; Hope, S; N?rland, T; Elvs?shagen, T; D?rum, E; Rustan, ?; Valstad, M; Rezvaya, L; Lishaugen, H; Stens?nes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G

2017-01-01

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin?s dose?response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequ...

Efficacy of topical Rose (Rosa damascena Mill.) oil for migraine headache: A randomized double-blinded placebo-controlled cross-over trial.

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Niazi, Maria; Hashempur, Mohammad Hashem; Taghizadeh, Mohsen; Heydari, Mojtaba; Shariat, Abdolhamid

2017-10-01

To evaluate the effect of topical formulation of Rosa damascena Mill. (R. damascena) oil on migraine headache, applying syndrome diffrentiation model. Forty patients with migraine headache were randomly assigned to 2 groups of this double-blind, placebo-controlled cross-over trial. The patients were treated for the first 2 consecutive migraine headache attacks by topical R. damascena oil or placebo. Then, after one week of washout period, cross-over was done. Pain intensity of the patients' migraine headache was recorded at the beginnig and ten-sequence time schadule of attacks up to 24h. In addition, photophobia, phonophobia, and nausea and/or vomitting (N/V) of the patients were recorded as secondary outcomes. Finally, gathered data were analysed in a syndrome differentiation manner to assess the effect of R. damascena oil on Hot- and Cold-type migraine headache. Mean pain intensity of the patients' migraine headache in the different time-points after R. damascena oil or placebo use, was not significantly different. Additionally, regarding mean scores of N/V, photophobia, and phonophobia severity of the patients, no significant differences between the two groups were observed. Finally, applying syndrome differentiation model, the mean score of migraine headache pain intensity turned out to be significantly lower in patients with "hot" type migraine syndrome at in 30, 45, 60, 90, and 120min after R. damascena oil application compared to "cold" types (P values: 0.001, 0.001, <0.001, <0.001, and 0.02; respectively). It seems that syndrome differentiation can help in selection of patients who may benefit from the topical R. damascena oil in short-term relief of pain intensity in migraine headache. Further studies of longer follow-up and larger study population, however, are necessitated for more scientifically rigorous judgment on efficacy of R. damascena oil for patients with migraine headache. Copyright © 2017 Elsevier Ltd. All rights reserved.

Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia

DEFF Research Database (Denmark)

Volkmann, H; Nørregaard, J; Jacobsen, Søren

1997-01-01

The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial. There was no sign......The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial.......17) and slight improvement only on fatigue, quality of sleep, morning stiffness, and on the Fibromyalgia Impact Questionnaire for pain. No effect could be observed on isokinetic muscle strength, Zerrsen self-assessment questionnaire, and the face scale. No effect of SAMe in patients with FM was found...

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

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Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

2006-07-01

Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial.

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Amen, Daniel G; Taylor, Derek V; Ojala, Kristine; Kaur, Jasleen; Willeumier, Kristen

2013-01-01

In a prior open trial of professional football players who displayed the effects of traumatic brain injury, the current reserach team reported significant improvements in clinical symptoms, neuropsychological testing and regional cerebral blood flow (rCBF) following the use of brain-directed nutrients (BDNs) and lifestyle interventions. The current study intended to determine whether supplementation with BDNs improved rCBF and neuropsychological function in healthy individuals. The current study was a randomized, doubleblind, placebo-controlled, crossover trial, which was a more rigorous reseach design than the prior study and did not include lifestyle interventions. Participants underwent evaluation and testing at the Amen Clinics, Inc, a private medical facility in Newport Beach, CA. Thirty healthy adult (15 male and 15 female) participants were recruited from the community though local advertising and met the requirements for eligibility into the study. Twenty-five individuals completed the study, with dropout due to events unrelated to the study itself. The participants were randomly assigned to a treatment order for intervention, either placebo or brain supplements first. The BDNs treatment was comprised of three supplements: fish oil; a high-potency, multiple vitamin/mineral supplement; and a brainenhancement supplement. The placebo treatment was two supplements comprised of rice flour to replace the multiple vitamin/mineral complex and the brain-enhancement supplement and one supplement made of other oils to replace the fish-oil mixture. After 2 mo of this first intervention, a crossover intervention occurred for a final 2 mo, in which participants formerly receiving BDNs received a placebo treatment and participants formerly treated with placebo received the BDNs treatment. Primary outcome measures included (1) an analysis of the changes in rCBF using SPECT and (2) an assessment of the differences in cognitive and emotional function using the Micro

Orange Pomace Improves Postprandial Glycemic Responses: An Acute, Randomized, Placebo-Controlled, Double-Blind, Crossover Trial in Overweight Men

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C.-Y. Oliver Chen

2017-02-01

Full Text Available Orange pomace (OP, a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-controlled, double blind, crossover trial with 34 overweight men who consumed either a 255 g placebo (PLA, a low (35% OP (LOP, or a high (77% (HOP dose OP beverage with breakfast. Blood was collected at 0, 10, 20, 30, and 45 min and at 1, 1.5, 2, 3, 4, 5, 5.5, 6, 6.5, 7, and 8 h. Lunch was consumed after the 5.5-h blood draw. OP delayed the time (Tmax1 to the maximum concentration (Cmax1 of serum glucose during the 2-h period post breakfast by ≥36% from 33 (PLA to 45 (HOP and 47 (LOP min (p = 0.055 and 0.013, respectively. OP decreased post-breakfast insulin Cmax1 by ≥10% and LOP delayed the Tmax1 by 14 min, compared to PLA at 46 min (p ≤ 0.05. HOP reduced the first 2-h insulin area under concentration time curve (AUC by 23% compared to PLA. Thus, OP diminishes postprandial glycemic responses to a high carbohydrate/fat breakfast and the second meal in overweight men.

[Placebo-controlled trials in schizophrenia].

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Melamed, Yuval; Davidson, Michael; Bleich, Avi

2004-03-01

Clinical trials involving human subjects give rise to ethical and medico-legal dilemmas. Essential research of new drugs may potentially expose patients to ineffective medications or to placebo. The complexity of the problem increases when dealing with mentally ill patients, for whom, on the one hand there is no known cure for their disease, and on the other hand, it is sometimes questionable whether or not they are able to provide informed consent to participate in clinical trials. The Israel Psychiatric Association decided to develop a position paper on the subject of placebo-controlled clinical trials in schizophrenia patients. Discussion groups were established, and the available material in the professional literature was examined, with an emphasis on recent developments. The Declaration of Helsinki and its amendments were analyzed, and experts in the field were consulted. Clinical drug trials for development of new medications are essential in all fields of medicine, especially in psychiatry. The requirement for a placebo arm in pharmaceutical trials presents ethical and clinical dilemmas that are especially complicated with regard to mentally ill persons whose free choice and ability to provide informed consent may be questionable. However, we do not believe that this predicament justifies unconditional rejection of placebo use in psychiatry, when it may provide substantial benefit for some patients. Simultaneously, it is our duty to provide stringent restrictions that will enable strict supervision over the scientific, clinical and ethical aspects of the trials. We propose the following criteria for approval of pharmaceutical trials that include a placebo arm: scientific justification; clinical and ethical justification; provision of informed consent; recruitment of patients hospitalized voluntarily; prevention of harm; administration of additional potential therapeutic interventions; benefit to patients participating in the study; control and follow

Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

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MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

2007-12-01

In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

A brief history of placebos and clinical trials in psychiatry.

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Shorter, Edward

2011-04-01

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis

DEFF Research Database (Denmark)

Falah, M; Madsen, C; Holbech, J V

2012-01-01

sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well....... Twenty-seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample...... of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non...

Effects of Milnacipran on Neurocognition, Pain, and Fatigue in Fibromyalgia: A 13-Week, Randomized, Placebo-Controlled, Crossover Trial

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Kim, Jeong Lan; Rele, Shilpa; Marks, David M.; Masand, Prakash S.; Yerramsetty, Pallavi; Millet, Robert A.; Keefe, Richard S.

2013-01-01

Objective: To investigate whether milnacipran is safe and effective in improving cognitive function in patients with fibromyalgia. Method: Patients were randomly assigned to receive milnacipran or placebo for 6 weeks, followed by a 1-week washout and then crossover to the other arm for another 6 weeks. The overall trial lasted 13 weeks and was conducted between July 2011 and May 2013. Assessments were performed at each visit. Neurocognition was measured by the Brief Assessment of Cognition (BAC) and MATRICS. Pain was assessed by the visual analog scale (VAS) for pain. Global assessment of fibromyalgia symptoms was measured by the Fibromyalgia Impact Questionnaire (FIQ) and tender point examination. Depression was assessed by the Beck Depression Inventory (BDI). Fatigue was assessed by the Fatigue Severity Scale. Functional outcome was evaluated by the Health Assessment Questionnaire. The Clinical Global Impressions–Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Patients Clinical Global Impression of Change were used to measure the global impression of severity and improvement. Results: 26 subjects were screened, and 20 subjects completed the trial. The change in verbal memory (P = .001) and the composite T score (P = .044) of the BAC and the change in the attention-vigilance domain T score (P = .042) were significantly improved, but there were no differences between the drug and placebo groups. The changes in the CGI-S scores were not significant, but the changes in the Clinical Impression-Improvement (CGI-I) scores showed worsening in the placebo group at week 1 (P = .032), week 2 (P = .024), week 4 (P = .024), and week 6 (P = .60) compared to baseline. The change in FIQ scores was not significant. Conclusions: Milnacipran may have a potential role in the improvement of pain, disability, and mood. The effect of milnacipran on cognition in fibromyalgia needs further research. Trial Registration: ClinicalTrials.gov identifier: NCT01829243 PMID

Lack of functional benefit with glutamine versus placebo in Duchenne muscular dystrophy: a randomized crossover trial.

Directory of Open Access Journals (Sweden)

Elise Mok

Full Text Available Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD. We evaluated the functional benefit of 4 months oral glutamine in DMD.30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine, markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine, serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage, safety and oral nutrient intake. There was no improvement in the primary end point (walking speed or in secondary measures of muscle function (2-minute walk test, work, power in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated.This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise.(ClinicalTrials.gov NCT00296621.

Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study

Science.gov (United States)

Gunzler, Steven A.; Koudelka, Caroline; Carlson, Nichole E.; Pavel, Misha; Nutt, John G.

2011-01-01

Objective To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state. Design Randomized, double-blind, placebo-controlled, crossover clinical trial. Setting Academic movement disorders center. Patients Patients with Parkinson disease and motor fluctuations. Intervention Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (sub-threshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 μg/kg/h every 2 hours and 25 μg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 μg/kg/h every 2 hours and 100 μg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days. Main Outcome Measures Finger and foot tapping rates. Results There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P<.001) and trended toward increasing finger tapping compared with placebo infusions. Conclusions Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that pre-synaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease. PMID:18268187

Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA: A randomised placebo-controlled crossover trial

Directory of Open Access Journals (Sweden)

Richmond Stewart J

2008-09-01

Full Text Available Abstract Background Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis. Methods/Design The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual

The Effect of Korean Red Ginseng on Sexual Function in Premenopausal Women: Placebo-Controlled, Double-Blind, Crossover Clinical Trial

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Ho Seok Chung

2015-01-01

Full Text Available This study investigated whether Korean red ginseng (KRG extracts could improve sexual function in premenopausal women. Forty-one premenopausal women participated in this placebo-controlled, double-blind, and crossover clinical study with administration of either three ginseng capsules (1 g per capsule or placebo daily. After 8 weeks of medication of KRG or placebo, medication was changed for the subjects to placebo or KRG after 2 weeks of washout period. The efficacy of KRG extracts was measured by using Female Sexual Function Index (FSFI. Results. Twenty-three women completed the study. Total FSFI scores increased after KRG treatment (from 20.13±2.87 to 23.98±4.10, p=0.015 and placebo treatment (from 20.06±2.64 to 23.78±3.28, p=0.003. However, this change was not significantly different between the two groups (p=0.702. KRG treatment significantly improved sexual desire, arousal, orgasm, and satisfaction domains; however, there was no treatment effect compared with placebo. There was a case of gastric discomfort after taking KRG extracts. Oral administration of KRG extracts improved sexual function in premenopausal women; however, there were no statistical significant changes compared to placebo. It implies that KRG extracts have a substantial placebo effect in premenopausal women with sexual dysfunction.

Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

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Libov, Igor; Miodownik, Chanoch; Bersudsky, Yuly; Dwolatzky, Tzvi; Lerner, Vladimir

2007-07-01

Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. ClinicalTrials.gov identifier NCT00190008.

Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial.

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Nunes, Luciana Vargas Alves; Lacaz, Fernando Sargo; Bressan, Rodrigo Affonseca; Nunes, Sandra Odebrecht Vargas Alves; Mari, Jair de Jesus

2013-04-01

INTRODUCTION.: Evidence is accumulating to support the presence of erectile dysfunction in patients with schizophrenia. This dysregulation may be amenable to therapeutic intervention to improve adherence and quality of life of patients who suffer from schizophrenia and schizoaffective disorders. AIM.: We aimed to evaluate the use of adjunctive medication lodenafil for the treatment of erectile dysfunction in outpatients with schizophrenia and spectrum. METHODS.: The design was a randomized, double-blind, crossover, placebo-controlled trial with lodenafil and it was carried at the Schizophrenia Outpatients Program. MAIN OUTCOME MEASURES.: The measures used to assess sexual dysfunction were Arizona Sexual Experiences Scale (ASEX) and International Index of Erectile Function (IIEF). The Positive and Negative Syndrome Scale (PANSS) and the Quality of Life Scale (QLS) were also used. The measures included the levels of prolactin, estradiol, luteinizing hormone, sex hormone-binding globulin, free testosterone, and total testosterone at baseline and end point. Lodenafil and placebo pills were used by the patients for 16 weeks. RESULTS.: Fifty male outpatients fulfilled the criteria and 94% of the participants completed the study. Lodenafil and placebo produced improvement in ASEX, IIEF scale, PANSS, and QLS, and there was no statistical difference between lodenafil and placebo groups in all sexual domains in the results of PANSS and QLS and in the results of hormone levels. CONCLUSION.: These results indicate that both lodenafil and placebo were effective in the treatment of erectile dysfunction for schizophrenia. Placebo effect is very important in patients with schizophrenia and this study showed the importance of discussing sexuality and trying to treat these patients. Further studies designed to test treatments of erectile dysfunction in patients who suffer from schizophrenia are necessary. © 2013 International Society for Sexual Medicine.

Bright Light for Weight Loss: Results of a Controlled Crossover Trial

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Konstantin V. Danilenko

2013-02-01

Full Text Available Objective: To investigate whether bright light treatment can reduce body mass in overweight subjects irrespective of their seasonal (= light dependence. Methods: A crossover, placebo-controlled, randomized clinical trial was performed between November and April in Novosibirsk, Russia (55° N. The trial comprised a 3-week in-home session of morning bright light treatment using a device of light-emitting diodes and a 3-week placebo session by means of a deactivated ion generator, separated by an off-protocol period of at least 23 days. The number of placebo and light sessions was matched with respect to season. Data were obtained from 34 overweight women, aged 20-54 years, 10 were seasonal-dependent according to the Seasonal Pattern Assessment Questionnaire. Weekly measures included body weight, percentage body fat by bioimpedancemetry, and subjective scores (appetite, mood, energy levels. Results: Motivation and expectation towards weight loss were similar for the two intervention sessions. With light, compared to the placebo session, weight did not reduce significantly, but percentage fat, fat mass, and appetite were significantly lower (average fat reduction 0.35 kg. The latter two results remained significant after excluding seasonal-dependent subjects from the analysis. Irrespective of the type of intervention, seasonal-dependent subjects had greater weight and fat mass changes during treatment (decline p 0.036 or between sessions (regain p 0.003. Photoperiod (p = 0.0041, air temperature to a lesser extent (p = 0.012, but not sunshine (p = 0.29 was associated with the weight change (greater weight reduction if the second session was in spring. Conclusion: Morning bright light treatment reduces body fat and appetite in overweight women and may be included in weight control programs.

Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial

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Pouryaghoub Gholamreza

2008-10-01

Full Text Available Abstract Background Night work is associated with disturbed sleep and wakefulness, particularly in relation to the night shift. Circadian rhythm sleep disorders are characterized by complaints of insomnia and excessive daytime sleepiness that are primarily due to alterations in the internal circadian timing system or a misalignment between the timing of sleep and the 24-h social and physical environment. Methods We evaluated the effect of oral intake of 5 mg melatonin taken 30 minutes before night time sleep on insomnia parameters as well as subjective sleep onset latency, number of awakenings, and duration of sleep. A double-blind, randomized, placebo-controlled crossover study with periods of 1 night and washouts of 4 days comparing melatonin with placebo tablets was conducted. We tried to improve night-time sleep during recovery from night work. Participants were 86 shift-worker nurses aged 24 to 46 years. Each participant completed a questionnaire immediately after awakening. Results Sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time. No adverse effects of melatonin were noted during the treatment period. Conclusion Melatonin may be an effective treatment for shift workers with difficulty falling asleep.

Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study.

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Thomson, M A; Jenkins, H R; Bisset, W M; Heuschkel, R; Kalra, D S; Green, M R; Wilson, D C; Geraint, M

2007-11-01

To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. Randomised, double blind, placebo controlled crossover trial, with two 2-week treatment periods separated by a 2-week placebo washout. Six UK paediatric departments. 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting > or =3 months), defined as or =25% of bowel movements with straining; > or =25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; pPEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (pPEG+E (41%) and placebo during treatment (45%). PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children.

Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia

DEFF Research Database (Denmark)

Volkmann, H; Nørregaard, J; Jacobsen, Søren

1997-01-01

The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial. There was no sign......The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial....... There was no significant difference in improvement in the primary outcome: tender point change between the two treatment groups. There was a tendency towards statistical significance in favour of SAMe on subjective perception of pain at rest (p = 0.08), pain on movement (p = 0.11), and overall well-being (p = 0.......17) and slight improvement only on fatigue, quality of sleep, morning stiffness, and on the Fibromyalgia Impact Questionnaire for pain. No effect could be observed on isokinetic muscle strength, Zerrsen self-assessment questionnaire, and the face scale. No effect of SAMe in patients with FM was found...

Chronic Effects of a Wild Green Oat Extract Supplementation on Cognitive Performance in Older Adults: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

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Narelle M. Berry

2012-05-01

Full Text Available Background and aim: Preliminary evaluation of a wild green oat extract (WGOE (Neuravena^® ELFA^®955, Frutarom, Switzerland revealed an acute cognitive benefit of supplementation. This study investigated whether regular daily WGOE supplementation would result in sustained cognitive improvements. Method: A 12-week randomised, double-blind, placebo-controlled cross-over trial of WGOE supplementation (1500 mg/day versus placebo was undertaken in 37 healthy adults aged 67 ± 0.8 years (mean ± SEM. Cognitive assessments included the Stroop colour-word test, letter cancellation, the rule-shift task, a computerised multi-tasking test battery and the trail-making task. All assessments were conducted in Week 12 and repeated in Week 24 whilst subjects were fasted and at least 18 h after taking the last dose of supplement. Result: Chronic WGOE supplementation did not affect any measures of cognition. Conclusion: It appears that the cognitive benefit of acute WGOE supplementation does not persist with chronic treatment in older adults with normal cognition. It remains to be seen whether sustained effects of WGOE supplementation may be more evident in those with mild cognitive impairment.

Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled, cross-over trial.

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Jørgensen, Mette Rose; Keller, Mette Kirstine; Kragelund, Camilla; Hamberg, Kristina; Ericson, Dan; Nielsen, Claus Henrik; Twetman, Svante

2016-07-01

To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. The study group consisted of 47 healthy adults (18-32 years) who volunteered for a randomized, double-blind, placebo-controlled, cross-over trial after informed consent. During intervention, the subjects ingested two lozenges per day containing two strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo lozenges. The intervention and wash-out periods were 3 weeks. Saliva samples were collected at baseline, immediately after each intervention period and 3 weeks post-intervention. ELISA was used to measure sIgA and luminex technology was used to measure the interleukins (IL)-1β, IL-6, IL-8 and IL-10. For statistical analyses a mixed ANOVA model was employed to calculate changes in the salivary outcome variables. Forty-one subjects completed the study and reported a good compliance. No significant differences in the concentrations of salivary sIgA or cytokines were recorded between the L. reuteri and placebo interventions or between baseline and 3 weeks post-intervention levels. No side- or adverse effects were reported. Supplementation with two strains of the probiotic L. reuteri did not affect sIgA or cytokine levels in whole saliva in healthy young adults. The results thereby indicate that daily oral supplementation with L. reuteri do not seem to modulate the salivary oral immune response in healthy young subjects (ClinicalTrials.gov NCT02017886).

Efficacy of omeprazole on cough, pulmonary function and quality of life of patients with sulfur mustard lung injury: A placebo-control, cross-over clinical trial study

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Mohammad Hossein Emami

2014-01-01

Full Text Available Background: Gastro-esophageal reflux disease (GERD is prevalent and related to more severe disease in patients with respiratory problems. We evaluated the effects of antireflux therapy in warfare victims of exposure to Mustard gas with chronic cough. Materials and Methods: This randomized, double-blind, placebo-controlled, cross-over study was conducted on 45 cases of sulfur mustard injury with chronic cough (≥8 weeks and GERD. Patients were randomized into two groups, receiving either 20 mg twice daily omeprazole-placebo (OP or matching placebo (placebo-omeprazole [PO] for 4 months, followed by a 1-month washout period and the alternative treatment for 4 months. Assessments included GERD and cough, quality of life, and pulmonary function using spirometry. Leicester Cough Questionnaire and SF-36 were used for measuring quality of life. Results: Patients in the OP group experienced a more decrease than those in the PO group in severity of Leicester cough scores during the first 4-month of trial. After crossing the groups, the OP group experienced an increase (P = 0.036 and the PO group experienced a nonsignificant decrease (P = 0.104 in the severity of scores. The OP group also experienced improvement in GERD symptoms and quality of life at the end of the trial, but changes in the PO group was not significant. There was no significant change in respiratory function indices in any groups. Conclusion: Long-term treatment with high-dose omeprazole improved GERD as well as cough, and quality of life, but not changed respiratory function indices in sulfur mustard injured cases with respiratory symptoms.

Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan.

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Norio Sugawara

Full Text Available Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs.The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan.Using a cross-sectional design, we recruited patients (n = 251 aged 47.7±13.2 (mean±SD with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials.The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation.Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.

Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study.

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Geisthoff, Urban W; Seyfert, Ulrich T; Kübler, Marcus; Bieg, Birgitt; Plinkert, Peter K; König, Jochem

2014-09-01

Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months. 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p=0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p=0.0031), as compared to the placebo period. No severe side effects were observed. Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008-001 and ClinicalTrials.gov NCT01031992). Copyright © 2014 Elsevier Ltd. All rights reserved.

Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.

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de los Santos, A R; Zmijanovich, R; Pérez Macri, S; Martí, M L; Di Girolamo, G

2001-01-01

We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

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Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-11-01

Kale ( Brassica oleracea var. acephala ), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (C max ; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); Pkale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

Does different information disclosure on placebo control affect blinding and trial outcomes? A case study of participant information leaflets of randomized placebo-controlled trials of acupuncture

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Soyeon Cheon

2018-01-01

Full Text Available Abstract Background While full disclosure of information on placebo control in participant information leaflets (PILs in a clinical trial is ethically required during informed consent, there have been concerning voices such complete disclosures may increase unnecessary nocebo responses, breach double-blind designs, and/or affect direction of trial outcomes. Taking an example of acupuncture studies, we aimed to examine what participants are told about placebo controls in randomized, placebo-controlled trials, and how it may affect blinding and trial outcomes. Methods Authors of published randomized, placebo-controlled trials of acupuncture were identified from PubMed search and invited to provide PILs for their trials. The collected PILs were subjected to content analysis and categorized based on degree of information disclosure on placebo. Blinding index (BI as a chance-corrected measurement of blinding was calculated and its association with different information disclosure was examined. The impact of different information disclosure from PILs on primary outcomes was estimated using a random effects model. Results In 65 collected PILs, approximately 57% of trials fully informed the participants of placebo control, i.e. full disclosure, while the rest gave deceitful or no information on placebo, i.e. no disclosure. Placebo groups in the studies with no disclosure tended to make more opposite guesses on the type of received intervention than those with disclosure, which may reflect wishful thinking (BI −0.21 vs. −0.16; p = 0.38. In outcome analysis, studies with no disclosure significantly favored acupuncture than those with full disclosure (standardized mean difference − 0.43 vs. −0.12; p = 0.03, probably due to enhanced expectations. Conclusions How participants are told about placebos can be another potential factor that may influence participant blinding and study outcomes by possibly modulating patient expectation. As we

A human model of inflammatory cardio-metabolic dysfunction; a double blind placebo-controlled crossover trial

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Mehta Nehal N

2012-06-01

Full Text Available Abstract Background Chronic inflammation may contribute to insulin resistance (IR, metabolic syndrome and atherosclerosis although evidence of causality is lacking in humans. We hypothesized that very low-dose experimental endotoxemia would induce adipose tissue inflammation and systemic IR during a low-grade but asymptomatic inflammatory response and thus provide an experimental model for future tests of pharmacologic and genomic modulation of cardio-metabolic traits in humans. Methods Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8 were randomized in a double-masked, placebo-controlled, crossover study to separate 36-hour inpatient visits (placebo versus intravenous-LPS 0.6 ng/kg. We measured clinical symptoms via the McGill pain questionnaire and serial vital signs. Plasma and serum were collected for measurement of cytokines, C-reactive protein, insulin and glucose, serial whole blood & subcutaneous adipose tissue mRNA expression were measured by real-time PCR. HOMA-IR, a well-validated measure of IR was calculated to estimate insulin resistance, and frequently sampled intravenous glucose tolerance testing (FSIGTT was performed to confirm an insulin resistant state. We performed ANOVA and within subject ANOVA to understand the differences in cytokines, adipose tissue inflammation and IR before and after LPS or placebo. Results There was no significant difference between placebo and LPS in clinical responses of symptom scores, body temperature or heart rate. However, low-dose endotoxemia induced a rapid and transient 25-fold induction of plasma TNF-alpha and 100-fold increase in plasma IL-6 (Figure 1B (p p p = 0.01 increased with MCP-1 (peak 10-fold, F = 5.6, p p p p  Conclusions We present a low dose human endotoxemia model of inflammation which induces adipose tissue inflammation and systemic insulin resistance in the absence of overt clinical response. Such a model has the potential

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

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Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Coughlin, Catherine G; Leckman, James F; Bloch, Michael H

2015-09-01

Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant

Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

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Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

2015-03-01

T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents

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Johnson, Mats; Ostlund, Sven; Fransson, Gunnar; Kadesjo, Bjorn; Gillberg, Christopher

2009-01-01

Objective: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). Method: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD…

Clinical trial of modulatory effects of oxytocin treatment on higher-order social cognition in autism spectrum disorder: a randomized, placebo-controlled, double-blind and crossover trial.

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Preckel, Katrin; Kanske, Philipp; Singer, Tania; Paulus, Frieder M; Krach, Sören

2016-09-21

Autism spectrum disorders are neurodevelopmental conditions with severe impairments in social communication and interaction. Pioneering research suggests that oxytocin can improve motivation, cognition and attention to social cues in patients with autism spectrum disorder. The aim of this clinical trial is to characterize basic mechanisms of action of acute oxytocin treatment on neural levels and to relate these to changes in different levels of socio-affective and -cognitive functioning. This clinical study is a randomized, double-blind, cross-over, placebo-controlled, multicenter functional magnetic resonance imaging study with two arms. A sample of 102 male autism spectrum disorder patients, diagnosed with Infantile Autistic Disorder (F84.0 according to ICD-10), Asperger Syndrome (F84.5 according to ICD-10), or Atypical Autism (F84.1 according to ICD-10) will be recruited and will receive oxytocin and placebo nasal spray on two different days. Autism spectrum disorder patients will be randomized to determine who receives oxytocin on the first and who on the second visit. Healthy control participants will be recruited and case-control matched to the autism spectrum disorder patients. The primary outcome will be neural network activity, measured with functional magnetic resonance imaging while participants perform socio-affective and -cognitive tasks. Behavioral markers such as theory of mind accuracy ratings and response times will be assessed as secondary outcomes in addition to physiological measures such as skin conductance. Trait measures for alexithymia, interpersonal reactivity, and social anxiety will also be evaluated. Additionally, we will analyze the effect of oxytocin receptor gene variants and how these potentially influence the primary and secondary outcome measures. Functional magnetic resonance imaging assessments will take place at two time points which will be scheduled at least two weeks apart to ensure a sufficient wash-out time after oxytocin

Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults Participating in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

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Holscher, Hannah D; Bauer, Laura L; Gourineni, Vishnupriya; Pelkman, Christine L; Fahey, George C; Swanson, Kelly S

2015-09-01

Prebiotics resist digestion, providing fermentable substrates for select gastrointestinal bacteria associated with health and well-being. Agave inulin differs from other inulin type fibers in chemical structure and botanical origin. Preclinical animal research suggests these differences affect bacterial utilization and physiologic outcomes. Thus, research is needed to determine whether these effects translate to healthy adults. We evaluated agave inulin utilization by the gastrointestinal microbiota by measuring fecal fermentative end products and bacterial taxa. A randomized, double-blind, placebo-controlled, 3-period, crossover trial was undertaken in healthy adults (n = 29). Participants consumed 0, 5.0, or 7.5 g agave inulin/d for 21 d with 7-d washouts between periods. Participants recorded daily dietary intake; fecal samples were collected during days 16-20 of each period and were subjected to fermentative end product analysis and 16S Illumina sequencing. Fecal Actinobacteria and Bifidobacterium were enriched (P inulin/d, respectively, compared with control. Desulfovibrio were depleted 40% with agave inulin compared with control. Agave inulin tended (P inulin (g/kcal) and Bifidobacterium (r = 0.41, P inulin/d) per kilocalorie was positively associated with fecal butyrate (r = 0.30, P = 0.005), tended to be positively associated with Bifidobacterium (r = 0.19, P = 0.08), and was negatively correlated with Desulfovibrio abundance (r = -0.31, P = 0.004). Agave inulin supplementation shifted the gastrointestinal microbiota composition and activity in healthy adults. Further investigation is warranted to determine whether the observed changes translate into health benefits in human populations. This trial was registered at clinicaltrials.gov as NCT01925560. © 2015 American Society for Nutrition.

Efficacy and safety of premedication with single dose of oral pregabalin in children with dental anxiety: A randomized double-blind placebo-controlled crossover clinical trial

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Tahereh Eskandarian

2015-01-01

Full Text Available Background: Dental anxiety is a relatively frequent problem that can lead to more serious problems such as a child entering a vicious cycle as he/she becomes reluctant to accept the required dental treatments. The aim of this randomized double-blind clinical trial study was to evaluate the anxiolytic and sedative effect of pregabalin in children. Materials and Methods: Twenty-five children were randomized to a double-blind placebo-controlled crossover clinical trial. Two visits were scheduled for each patient. At the first visit, 75 mg pregabalin or placebo was given randomly, and the alternative was administered at the next visit. Anxiolytic and sedative effects were measured using the visual analogue scale. The child′s behavior was rated with the Frankl behavioral rating scale and the sedation level during the dental procedure was scored using the Ramsay sedation scale. The unpaired, two-tailed Student′s t-test was used to compare the mean changes of visual analog scale (VAS for anxiety in the pregabalin group with that of the placebo group. A repeated measures MANOVA model was used to detect differences in sedation level in the pregabalin and placebo groups regarding the interaction of 3-time measurements; sub-group analysis was performed using Student′s t-test. The Mann-Whitney U-test was used to analyze the nonparametric data of the Frankl and Ramsay scales. A P < 0.05 was considered significant. Results: The reduction of the VAS-anxiety score from 2 h post-dose was statistically significant in the pregabalin group. From 2 h to 4 h post-dose, the VAS-sedation score increased significantly in the pregabalin group. The child′s behavior rating was not significantly different between the groups. The number of "successful" treatment visits was higher in the pregabalin group compared to the placebo group. Conclusion: Significant anxiolytic and sedative effects can be anticipated 2 h after oral administration of pregabalin without serious

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

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Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

2017-05-23

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η 2 =0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children.

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Lamport, Daniel J; Lawton, Clare L; Merat, Natasha; Jamson, Hamish; Myrissa, Kyriaki; Hofman, Denise; Chadwick, Helen K; Quadt, Frits; Wightman, JoLynne D; Dye, Louise

2016-03-01

Daily consumption of Concord grape juice (CGJ) over 3-4 mo has been shown to improve memory function in adults with mild cognitive impairment and reduce blood pressure in hypertensive adults. These benefits likely result from the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus, we examined the potential beneficial effect of CGJ in individuals with somewhat stressful and demanding lifestyles. We sought to examine the effects of the daily consumption of CGJ for 12 wk on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. Twenty-five healthy mothers (aged 40-50 y) of preteen children who were employed for ≥30 h/wk consumed 12 ounces (355 mL) of either CGJ (containing 777 mg total polyphenols) or an energy-, taste-, and appearance-matched placebo daily for 12 wk according to a randomized crossover design with a 4-wk washout. Verbal and spatial memory, executive function, attention, blood pressure, and mood were assessed at baseline and at 6 and 12 wk. Immediately after the cognitive battery, a subsample of 17 women completed a driving performance assessment at the University of Leeds Driving Simulator. The 25-min driving task required participants to match the speed and direction of a lead vehicle. Significant improvements in immediate spatial memory and driving performance were observed after CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. Cognitive benefits associated with the long-term consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond the cessation of flavonoid consumption, and future studies should carefully consider the length of washout within

Gabapentin in traumatic nerve injury pain: A randomized, double-blind, placebo-controlled, cross-over, multi-center study

DEFF Research Database (Denmark)

Gordh, Torsten E; Stubhaug, Audun; Jensen, Troels S

2008-01-01

A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400mg/day. The study comprised a run...

The challenge of recruiting patients into a placebo-controlled surgical trial

DEFF Research Database (Denmark)

Hare, Kristoffer B; Lohmander, L Stefan; Roos, Ewa M.

2014-01-01

BACKGROUND: Randomized placebo-controlled trials represent the gold standard in evaluating healthcare interventions but are rarely performed within orthopedics. Ethical concerns or well-known challenges in recruiting patients for surgical trials in general have been expressed and adding a placebo...

Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial.

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Faridi, Zubaida; Njike, Valentine Yanchou; Dutta, Suparna; Ali, Ather; Katz, David L

2008-07-01

Studies suggest cardioprotective benefits of dark chocolate containing cocoa. This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.

The effect of levetiracetam on focal nocturnal epileptiform activity during sleep--a placebo-controlled double-blind cross-over study.

Science.gov (United States)

Larsson, Pål Gunnar; Bakke, Kristin A; Bjørnæs, Helge; Heminghyt, Einar; Rytter, Elisif; Brager-Larsen, Line; Eriksson, Ann-Sofie

2012-05-01

Electric Status Epilepticus during Sleep (ESES) occurs in children with and without epilepsy. It may be related to disturbances as autism spectrum disorder, attention-deficit hyperactivity disorder and acquired aphasia (Landau-Kleffner syndrome). Antiepileptic drug (AED) treatment has been reported in small studies without placebo control. This study was designed to assess AED effect in a placebo-controlled double-blind cross-over study. Levetiracetam (LEV) was chosen based on clinical evidence. Eighteen patients fulfilled the inclusion criteria. The mean spike index at baseline was 56, falling to a mean of 37 at the end of the LEV treatment period. Assessed with a 2-way ANOVA, there is a significant treatment effect (pdouble-blind cross-over study for any AED in patients with ESES. The effect of LEV is comparable with its effect in treatment of epileptic seizures. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

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Nakato, Rui; Manabe, Noriaki; Shimizu, Sayako; Hanayama, Kozo; Shiotani, Akiko; Hata, Jiro; Haruma, Ken

2017-01-01

The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD. © 2017 S. Karger AG, Basel.

Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design

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Gao Joseph

2010-06-01

Full Text Available Abstract Background Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX was assessed in adults (18-55 years with attention-deficit/hyperactivity disorder (ADHD using the simulated adult workplace environment. Methods After open-label dose optimization (4-week with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP total score (attempted+correct measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary and at each time point vs placebo (secondary, and ADHD Rating Scale IV (ADHD-RS-IV with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs, vital signs, and electrocardiograms. Results Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P P ≤ .0017 for each time point and change from predose (P P Conclusions LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours to last (14 hours postdose time point vs placebo in adults with ADHD. Trial Registration ClinicalTrials.gov Identifier: NCT00697515 Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX in Adults With Attention-Deficit Hyperactivity Disorder (ADHD http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1

An algorithm for evaluating the ethics of a placebo-controlled trial.

Science.gov (United States)

Amdur, R J; Biddle, C J

2001-10-20

The purpose of this article is to clarify the decision points that are important to consider when evaluating the ethics of a placebo-controlled trial. The ethical requirements for research involving human subjects are reviewed, and the rationale for and potential problems with concomitant placebo control are explained. A series of case discussions are used to illustrate each decision point. The critical decision points in the evaluation of the ethics of a placebo-controlled trial are as follows: (i) Is placebo being used in place of standard therapy? (ii) Is standard therapy likely to be effective? (iii) Is the toxicity of standard therapy such that patients routinely refuse this treatment? (iv) Could the use of placebo result in severe suffering or irreversible harm? (v) Is the variability in the placebo response such that it is reasonable to consider other options for the control group? (vi) Would a reasonable person with an average degree of altruism and risk aversiveness agree to participate in this study? The algorithm presented in this article gives researchers and research monitors (such as Institutional Review Board members) the tools they need to evaluate the ethics of a study that uses concomitant placebo control. Copyright 2001 Wiley-Liss, Inc.

1% hydrocortisone ointment is an effective treatment of pruritus ani: a pilot randomized controlled crossover trial.

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Al-Ghnaniem, R; Short, K; Pullen, A; Fuller, L C; Rennie, J A; Leather, A J M

2007-12-01

Pruritus ani (PA) is a common condition which is difficult to treat in the absence of obvious predisposing factors. There is paucity of evidence-based guidelines on the treatment of this condition. We examined whether 1% hydrocortisone ointment is an effective treatment for PA. A pilot randomized, double-blind, placebo-controlled, crossover trial was carried out. Eleven patients consented to take part in the trial and ten completed the study. After a 2-week run-in period, patients with primary PA were randomly allocated to receive 1% hydrocortisone ointment or placebo for 2 weeks followed by the opposite treatment for a further 2-week period. There was a washout period of 2 weeks between treatments. The primary outcome measure was reduction in itch using a visual analogue score (VAS). The secondary outcome measures were improvement in quality of life measured using a validated questionnaire (Dermatology Life Quality Index, DLQI) and improvement in clinical appearance of the perianal skin using the Eczema Area and Severity Index (EASI) score. Treatment with 1% hydrocortisone ointment resulted in a 68% reduction in VAS compared with placebo (P=0.019), a 75% reduction in DLQI score (P=0.067), and 81% reduction in EASI score (P=0.01). A short course of mild steroid ointment is an effective treatment for PA.

Resveratrol does not influence metabolic risk markers related to cardiovascular health in overweight and slightly obese subjects: a randomized, placebo-controlled crossover trial.

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Sanne M van der Made

Full Text Available In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein metabolism, but human studies specifically designed to examine these effects are lacking.The primary outcome parameter of this study in overweight and slightly obese subjects was the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and markers for inflammation and endothelial function.This randomized, placebo-controlled crossover study was conducted in 45 overweight and slightly obese men (n = 25 and women (n = 20 with a mean age of 61 ± 7 years. Subjects received in random order resveratrol (150 mg per day or placebo capsules for 4 weeks, separated by a 4-week wash-out period. Fasting blood samples were collected at baseline and at the end of each intervention period.Compliance was excellent as indicated by capsule count and changes in resveratrol and dihydroresveratrol concentrations. No difference between resveratrol and placebo was found in any of the fasting serum or plasma metabolic risk markers (mean ± SD for differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 ± 0.12 g/L (P = 0.791, apoB100; -0.01 ± 0.11 g/L (P = 0.545, HDL cholesterol; 0.00 ± 0.09 mmol/L (P = 0.721, LDL cholesterol -0.03 ± 0.57 mmol/L (P = 0.718, triacylglycerol; 0.10 ± 0.54 mmol/L (P = 0.687, glucose; -0.08 ± 0.28 mmol/L (P = 0.064, insulin; -0.3 ± 2.5 mU/L (P = 0.516. Also, no effects on plasma markers for inflammation and endothelial function were observed. No adverse events related to resveratrol intake were observed.150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers related to cardiovascular health in overweight and slightly obese men and women. Effects on glucose metabolism warrant further study.ClinicalTrials.gov NCT01364961.

Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

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Burbank F

2014-02-01

Full Text Available Fred Burbank Salt Creek International Women's Health Foundation, San Clemente, CA, USA Purpose: To determine whether sham pads used as controls in randomized clinical trials of vibratory stimulation to treat patients with sleep loss associated with restless legs syndrome perform differently than placebo pills used in comparable restless legs syndrome drug trials. Patients and methods: Sham pad effect sizes from 66 control patients in two randomized clinical trials of vibratory stimulation were compared with placebo responses from 1,024 control patients in 12 randomized clinical drug trials reporting subjective sleep measurement scales. Control patient responses were measured as the standardized difference in means corrected for correlation between beginning and ending scores and for small sample sizes. Results: For parallel randomized clinical trials, sham effects in vibratory stimulation trials were not significantly different from placebo effects in drug trials (0.37 and 0.31, respectively, Qbetween subgroups =0.25, PQ≥0.62. Placebo effect sizes were significantly smaller in crossover drug trials than sham effect sizes in parallel vibratory stimulation trials (0.07 versus 0.37, respectively, Qbetween subgroups =4.59, PQ≤0.03 and placebo effect sizes in parallel drug trials (0.07 versus 0.31, respectively, Qbetween subgroups =5.50, PQ≤0.02. Conclusion: For subjective sleep loss assessments in parallel trials, sham pads in vibratory stimulation trials performed similarly to placebo pills in drug trials. Trial design (parallel versus crossover had a large influence on control effect sizes. Placebo pills in crossover drug trials had significantly smaller effect sizes than sham pads in parallel vibratory stimulation trials or placebo pills in parallel drug trials. Keywords: sham effect, placebo effect, trial design, crossover study, parallel study, counterstimulation

Developing a placebo-controlled trial in surgery: Issues of design, acceptability and feasibility

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McDonald AM

2011-02-01

Full Text Available Abstract Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons; plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists; three focus groups with anaesthetists (one national, two regional; 58 anaesthetists; two focus groups with members of the patient organisation Arthritis Care (7 participants; telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants; interviews with Chairs of UK ethics committees (6 individuals; postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists; two centre pilot (49 patients assessed. Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions proved easier than the method of anaesthesia (general anaesthesia. General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about

A randomized double blind crossover placebo-controlled clinical trial to assess the effects of a mouthwash containing chlorine dioxide on oral malodor

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Yokoyama Sayaka

2008-12-01

Full Text Available Abstract Background Previous research has shown the oxidizing properties and microbiological efficacies of chlorine dioxide (ClO2, however, its clinical efficacies on oral malodor have been evaluated only with organoleptic measurements (OM or sulphide monitors. No clinical studies have investigated the inhibitory effects of ClO2 on volatile sulfur compounds (VSCs using gas chromatography (GC. The aim of this study was to assess the inhibitory effects of a mouthwash containing ClO2 on morning oral malodor using OM and GC. Methods A randomized, double blind, crossover, placebo-controlled clinical trial was conducted among 15 healthy male volunteers, who were divided into 2 groups. In the first test phase, the group 1 subjects (N = 8 were instructed to rinse with the experimental mouthwash containing ClO2, and those in group 2 (N = 7 to rinse with the placebo mouthwash without ClO2. In the second test, phase after a one week washout period, each group used the opposite mouthwash. Oral malodor was evaluated before rinsing, right after rinsing and every 30 minutes up to 4 hours with OM, and concentrations of hydrogen sulfide (H2S, methyl mercaptan (CH3SH and dimethyl sulfide ((CH32S, the main VSCs of human oral malodor, were evaluated with GC. Results The baseline oral condition in the subjects in the 2 groups did not differ significantly. The mouthwash containing ClO2 improved morning bad breath according to OM and reduced concentrations of H2S, CH3SH and (CH32S according to GC up to 4 hours after rinsing. OM scores with ClO2 were significantly lower than those without ClO2 at all examination times. Significant reductions in the concentrations of the three kinds of VSCs measured by GC were also evident at all examination times. The concentrations of the three gases with ClO2 were significantly lower than those without ClO2 at most examination times. Conclusion In this explorative study, ClO2 mouthwash was effective at reducing morning malodor for 4

Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

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David J. White

2016-01-01

Full Text Available l-theanine (γ-glutamylethylamide is an amino acid found primarily in the green tea plant. This study explored the effects of an l-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG. Thirty-four healthy adults aged 18–40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the l-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of l-theanine.

Cross-Over Clinical Trials?

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Latif Gachkar

2017-01-01

Full Text Available Abstract Cross-Over Clinical Trials in comparison with Parallel groups clinical trials have some advantages such as control of confounding variables, small sample size, and short time to implement the research project. But this type of research has few essential limitations that discusses in this monogram.

Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.

Science.gov (United States)

Campbell, M K; Entwistle, V A; Cuthbertson, B H; Skea, Z C; Sutherland, A G; McDonald, A M; Norrie, J D; Carlson, R V; Bridgman, S

2011-02-21

Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this

Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study

DEFF Research Database (Denmark)

Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W

2009-01-01

BACKGROUND: Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. METHODS: In this randomised, double-blind, placebo-controlled crossover......, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly...... inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. FUNDING: Minster Pharmaceuticals; Lundbeck Foundation....

Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

NARCIS (Netherlands)

Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

2014-01-01

Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

Acute Garcinia mangostana (mangosteen) supplementation does not alleviate physical fatigue during exercise: a randomized, double-blind, placebo-controlled, crossover trial.

Science.gov (United States)

Chang, Chih-Wei; Huang, Tzu-Zung; Chang, Wen-Hsin; Tseng, Yi-Chun; Wu, Yu-Tse; Hsu, Mei-Chich

2016-01-01

The purple mangosteen (Garcinia mangostana), known as the "queen of fruit," is widely consumed and unique not only because of its outstanding appearance and flavor but also its remarkable and diverse pharmacological effects. The aim of the present study is to evaluate the effect of acute mangosteen supplementation on physical fatigue during exercise. A randomized, double-blind, placebo-controlled, crossover study was carried out by 12 healthy adults. The participants were randomly assigned to receive acute oral administration of either 250 mL of the mangosteen-based juice (supplementation treatment; 305 mg of α-mangostin and 278 mg of hydroxycitric acid) or a placebo (control treatment) 1 h before cycle ergometer exercise. Time to exhaustion, heart rate, Borg Rating of Perceived Exertion score, blood biochemical markers (namely ammonia, cortisol, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glucose, and lactate), muscle dynamic stiffness, and Profile of Mood States (POMS) were evaluated and recorded. The results showed all parameters we examined were significantly altered by the exercise challenge, which demonstrated they directly reflected the condition of fatigue. However, there were no differences between the two treatments besides a positive impact on the POMS examination. The occurrence of physical fatigue depends on multiple underlying mechanisms. We concluded that acute mangosteen supplementation had no impact on alleviating physical fatigue during exercise.

Effect of an herbal/botanical supplement on recovery from delayed onset muscle soreness: a randomized placebo-controlled trial.

Science.gov (United States)

Rynders, Corey A; Weltman, Judy Y; Rynders, Sara D; Patrie, James; McKnight, John; Katch, Frank I; Hertel, Jay; Weltman, Arthur

2014-01-01

We examined the effects of a proprietary herbal/botanical supplement (StemSport, Stemtech, San Clemente, CA.) suggested to increase circulating stem cells, decrease inflammation, and attenuate exercise induced muscle damage on recovery from delayed onset muscle soreness (DOMS). Sixteen subjects (male = 7, female = 9; age 23.8 ± 10 years; height 171.9 ± 10 cm, mass 72.2 ± 15 kg) were randomized in a crossover, double-blind, placebo controlled trial to receive a placebo or StemSport supplement (6150 mg/day) for 14 days. DOMS was induced on day 7 for both placebo and active conditions in the non-dominant elbow flexor group with repeated eccentric repetitions. Muscle swelling (biceps girth), elbow flexor isometric strength (hand held dynamometer), muscle pain/tenderness (visual analog scale), range of motion (active elbow flexion and extension), and inflammation (hsCRP, IL6, and TNF-α) were measured at baseline and at 24 h, 48 h, 72 h, and 168 h (1 week) post eccentric exercise. The crossover washout period was ≥14 days. No significant condition-by-time interactions between placebo and StemSport supplementation were observed with regard to measures of pain (p = 0.59), tenderness (p = 0.71), isometric strength (p = 0.32), elbow flexion (p = 0.45), muscle swelling (p = 0.90), or inflammation (p > 0.90). Decrements in elbow extension range of motion 48 h post-exercise were less after StemSport supplementation (Δ elbow extension 48 h post; StemSport, -2.0 deg; placebo, -10 deg; p = 0.003). These data suggest that compared to placebo, StemSport supplementation does not improve outcome measures related to muscle recovery after acute upper-arm induced DOMS.

Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.

Science.gov (United States)

Schwarz, Konstantin; Singh, Satnam; Parasuraman, Satish K; Rudd, Amelia; Shepstone, Lee; Feelisch, Martin; Minnion, Magdalena; Ahmad, Shakil; Madhani, Melanie; Horowitz, John; Dawson, Dana K; Frenneaux, Michael P

2017-09-08

In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans

DEFF Research Database (Denmark)

Fuglsang, S.; Madsen, Jan Lysgård

2008-01-01

emptying, small intestinal transit and colonic transit of a radiolabelled, 1600-kJ mixed liquid and solid meal ingested on day 2. RESULTS: Aprepitant did not change gastric retention at 15 min, gastric half emptying time, gastric mean transit time, time to small intestinal transit of 10%, small intestinal...... in healthy humans. METHODS: Twelve healthy volunteers participated in a crossover, double-blind study. In random order, each volunteer had a 125-mg capsule of aprepitant or placebo on day 1 followed by an 80-mg capsule of aprepitant or placebo on days 2-5. Gamma camera imaging was used to measure gastric...

Caffeine improves endurance in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study

DEFF Research Database (Denmark)

Buchard Nørager, Charlotte; Jensen, Martin Bach; Madsen, Mogens Rørbæk

2005-01-01

This study investigated the effect of caffeine on physical performance in healthy citizens aged ≥70 yr. The randomized, double-blind, placebo-controlled, crossover study was conducted in 15 men and 15 women recruited by their general practitioner. Participants abstained from caffeine for 48 h...... and were randomized to receive one capsule of placebo and then caffeine (6 mg/kg) or caffeine and then placebo with 1 wk in between. One hour after intervention, we measured reaction and movement times, postural stability, walking speed, cycling at 65% of expected maximal heart rate, perceived effort...... during cycling, maximal isometric arm flexion strength, and endurance. Analysis was by intention to treat, and P Caffeine increased cycling endurance by 25% [95% confidence interval (CI): 13–38; P = 0.0001] and isometric arm flexion endurance by 54% (95% CI: 29–83; P...

Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism.

Science.gov (United States)

Chez, Michael; Lepage, Christopher; Parise, Carol; Dang-Chu, Ashley; Hankins, Andrea; Carroll, Michael

2018-04-01

The aim of this exploratory study was to assess the safety and clinical effects of autologous umbilical cord blood (AUCB) infusion in children with idiopathic autism spectrum disorder (ASD). Twenty-nine children 2 to 6 years of age with a confirmed diagnosis of ASD participated in this randomized, blinded, placebo-controlled, crossover trial. Participants were randomized to receive AUCB or placebo, evaluated at baseline, 12, and 24 weeks, received the opposite infusion, then re-evaluated at the same time points. Evaluations included assessments of safety, Expressive One Word Picture Vocabulary Test, 4th edition, Receptive One Word Picture Vocabulary Test, 4th edition, Clinical Global Impression, Stanford-Binet Fluid Reasoning and Knowledge, and the Vineland Adaptive Behavior and Socialization Subscales. Generalized linear models were used to assess the effects of the response variables at the 12- and 24-week time periods under each condition (AUCB, placebo). There were no serious adverse events. There were trends toward improvement, particularly in socialization, but there were no statistically significant differences for any endpoints. The results of this study suggest that autologous umbilical cord infusions are safe for children with ASD. Tightly controlled trials are necessary to further progress the study of AUCB for autism. Stem Cells Translational Medicine 2018;7:333-341. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

Science.gov (United States)

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological

Memantine for prophylaxis of chronic tension-type headache--a double-blind, randomized, crossover clinical trial

DEFF Research Database (Denmark)

Lindelof, K; Bendtsen, L; Lindelof, K

2009-01-01

Treatment for chronic tension-type headache (CTTH) is unsatisfactory. Our aim was to investigate the efficacy of the N-methyl D-aspartate (NMDA) antagonist memantine in the prophylactic treatment of CTTH. We included 40 patients in a randomized, double-blind, placebo-controlled, crossover trial....... Memantine 20-40 mg/day or placebo was each given for 10 weeks separated by a 2-week wash-out period; 29 patients completed the study. The primary efficacy variable, area-under-the-headache curve (duration x intensity), did not differ between memantine (1352 +/- 927) and placebo (1449 +/- 976; P = 0.......10). Headache intensity in both sexes was significantly lower on a 0-10 verbal rating scale with memantine (3.8) than with placebo (4.1; P = 0.03). In women, area-under-the-headache curve was significantly lower with memantine (1343 +/- 919) than with placebo (1555 +/- 1019; P = 0.01). The most common side...

Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease.

Science.gov (United States)

Gaillard, S; Dupuis-Girod, S; Boutitie, F; Rivière, S; Morinière, S; Hatron, P-Y; Manfredi, G; Kaminsky, P; Capitaine, A-L; Roy, P; Gueyffier, F; Plauchu, H

2014-09-01

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder associated with abnormal angiogenesis and disabling epistaxis. Tranexamic acid (TA) has been widely used in the treatment of these severe bleeds but with no properly designed trial. To demonstrate the efficacy of TA in epistaxis in HHT patients and to explore its safety of use. A randomized, placebo-controlled, double-blind, cross-over trial was conducted. Participants were randomized to receive TA (3 g a day) then placebo or the opposite sequence. The main analysis compared intra-individual mean duration of epistaxis under TA vs. placebo on a log scale. The primary outcome was the mean duration of epistaxis per month, assessed with specific grids to be completed by participants. The number of epistaxis episodes was recorded as a secondary outcome. A total of 118 randomized patients contributed to the statistical analysis. The mean duration of epistaxis per month was significantly shorter with TA than placebo (0.19 on the log scale; SD = 0.07; P = 0.005), corresponding to a decrease of 17.3% (15.7 min) in the duration of epistaxis per month (CI 95%, 5.5-27.6). The median number of epistaxis episodes per month was 22.1 episodes in the placebo arm vs. 23.3 episodes in the TA arm. No thrombophlebitis was observed. In the ATERO study, we demonstrated a significant decrease in the duration of epistaxis in HHT patients taking TA. No safety issues were recorded in our cohort of patients. © 2014 International Society on Thrombosis and Haemostasis.

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension

DEFF Research Database (Denmark)

Gall, M A; Rossing, P; Skøtt, P

1992-01-01

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial...

The use of placebo control in clinical trials: An overview of the ...

African Journals Online (AJOL)

The use of placebo control in clinical trials: An overview of the ethical issues involved for the protection of human research participants. ... A placebo looks exactly like the experimental drugs in every respect both in appearance and wrappings ...

A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

Science.gov (United States)

2012-01-01

Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported. Results There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%). Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203 PMID:22800470

Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Stéphanie J.E. Becker

2014-09-01

 Younger patients with no college education, who believe their health can be controlled, are more likely to miss a research appointment when enrolled in a randomized placebo injection-controlled trial. 

Caffeine counteracts impairments in task-oriented psychomotor performance induced by chlorpheniramine: a double-blind placebo-controlled crossover study.

Science.gov (United States)

Kim, Sung-Wan; Bae, Kyung-Yeol; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Kim, Jong-Keun; Kang, Gaeun; Yoon, Jin-Sang

2013-01-01

This study aimed to evaluate the effects of chlorpheniramine on psychomotor performance and the counteracting effects of caffeine on those sedative antihistamine actions. Sixteen healthy young men participated in this study. Using a double-blind placebo-controlled crossover design, each subject was administered one of the following conditions in a random order with a one-week interval: 'placebo-placebo', '4 mg of chlorpheniramine-placebo', 'placebo-200 mg of caffeine' or '4 mg of chlorpheniramine-200 mg of caffeine'. Before and after the treatments, psychomotor functions were assessed using a battery of tests. Additionally, subjective responses were assessed using a visual analogue scale (VAS). Psychomotor performance changed over time in different ways according to the combination of study medications. In the 'chlorpheniramine-placebo' condition, reaction times of the compensatory tracking task were significantly impaired compared with the other three conditions. In addition, the number of omission errors of the continuous performance test were significantly greater compared with the 'placebo-caffeine' condition. However, the response pattern of the 'chlorpheniramine-caffeine' condition was not significantly different from that of the 'placebo-placebo' condition. Changes of VAS for sleepiness were significantly greater in the 'chlorpheniramine-placebo' condition compared with the other three conditions. In conclusion, chlorpheniramine significantly increases subjective sleepiness and objectively impairs psychomotor performance. However, caffeine counteracts these sedative effects and psychomotor impairments.

Actual driving performance and psychomotor function in healthy subjects after acute and subchronic treatment with escitalopram, mirtazapine, and placebo: a crossover trial.

Science.gov (United States)

Wingen, Marleen; Bothmer, John; Langer, Stefan; Ramaekers, Johannes G

2005-04-01

The effects of escitalopram 10 to 20 mg/day and mirtazapine 30 to 45 mg/day on actual driving and psychomotor performance of 18 healthy subjects were determined in a randomized, double-blind, placebo-controlled, multiple-dose, 3-way crossover trial. Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Subjects received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16, reflecting acute period, dose increase, and steady state, respectively, the Road Tracking Test was performed. The main parameter was standard deviation of lateral position. Psychomotor performance was also assessed on days 2, 9, and 16 by laboratory computer tasks. Subjective sleep quality was measured with the Groninger Sleep Quality Scale, and mood was measured by visual analogue scales. Treatment differences were apparent during the acute treatment period, in which subjects treated with mirtazapine 30 mg performed less well on the driving test as compared to placebo. The Divided Attention Task results also revealed a significant increase in tracking error after a single dose of mirtazapine 30 mg as compared to placebo. Mirtazapine decreased feelings of alertness and contentedness. Mirtazapine did not affect performance on days 9 and 16 of treatment. Escitalopram did not affect driving, psychomotor performance, or subjective mood throughout treatment. Driving performance, as well as psychomotor functioning, was not affected by escitalopram treatment in healthy subjects. Driving performance was significantly impaired after ingestion of mirtazapine 30 mg during the acute treatment period.

The effect of Lactobacillus brevis KB290 against irritable bowel syndrome: a placebo-controlled double-blind crossover trial

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Murakami Katsumi

2012-08-01

Full Text Available Abstract Background Irritable bowel syndrome (IBS is a functional disorder of the digestive tract that causes chronic abdominal symptoms. We evaluated the effects of Lactobacillus brevis KB290 (KB290, which has been demonstrated to be effective at improving bowel movements and the composition of intestinal microflora, on IBS symptoms. Methods We performed a placebo control double-blind cross matched trial. Thirty-five males and females (aged 6 years and above who had been diagnosed with IBS according to the Rome III criteria were divided into 2 groups, and after a 4-week pre-trial observation period, they were administered test capsules containing KB290 or placebo for 4 weeks (consumption period I. Then, the capsule administration was suspended for 4 weeks in both groups (washout period, before the opposite capsules were administered for a further 4 weeks (consumption period II. Fecal samples were collected on the first day of the pre-consumption observation period, the last day of consumption period I, the last day of the washout period, and the last day of consumption period II. In addition, the subjects’ IBS symptoms and quality of life (QOL and any adverse events that they experienced were evaluated. Results No significant difference in IBS symptoms was noted among the various periods. However, the mean QOL scores were improved during the test capsule consumption. The frequencies of watery and mushy feces were significantly lower in the test capsule consumption period than during the pre-consumption observation period, and the frequency of abdominal pain was significantly reduced in the test capsule consumption period compared with the other periods. The frequency of the genus Bifidobacterium was significantly higher, and that of the genus Clostridium was significantly lower, after the test capsule consumption than after the placebo consumption. The frequencies of the genera Lactobacillus, Bacteroides, and Enterococcus were also

Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

NARCIS (Netherlands)

de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

A double-blind placebo controlled trial of paroxetine in the ...

African Journals Online (AJOL)

A double-blind placebo controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa. Dan J. Stein, Michael Berk, Charl Els, Robin A. Emsley, Leon Gittelson, Don Wilson, Rosemary Oakes, Brian Hunter ...

Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.

Science.gov (United States)

Dower, James I; Geleijnse, Johanna M; Gijsbers, Lieke; Zock, Peter L; Kromhout, Daan; Hollman, Peter C H

2015-05-01

Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea). We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health. Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function. Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors. Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study

Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: a randomized placebo-controlled cross-over study using pharmacological fMRI.

Science.gov (United States)

Goudriaan, Anna E; Veltman, Dick J; van den Brink, Wim; Dom, Geert; Schmaal, Lianne

2013-02-01

Enhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. An fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. In the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil-induced increases in ACC and putamen activation. Enhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

Directory of Open Access Journals (Sweden)

Bone Kerry M

2009-06-01

Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

A randomized, double-blind, crossover, placebo-controlled clinical trial to assess effects of the single ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase on oral malodor.

Science.gov (United States)

Nakano, Manabu; Shimizu, Eiju; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

2016-03-22

The main components of oral malodor have been identified as volatile sulfur compounds (VSCs) including hydrogen sulfide (H2S) and methyl mercaptan (CH3SH). VSCs also play an important role in the progression of periodontal disease. The aim of the present study was to assess the effects of the single ingestion of a tablet containing 20 mg of lactoferrin, 2.6 mg of lactoperoxidase, and 2.6 mg of glucose oxidase on VSCs in the mouth. Subjects with VSCs greater than the olfactory threshold in their mouth air ingested a test or placebo tablet in two crossover phases. The concentrations of VSCs were monitored at baseline and 10 and 30 min after ingestion of the tablets using portable gas chromatography. Thirty-nine subjects were included in the efficacy analysis based on a full analysis set (FAS). The concentrations of total VSCs and H2S at 10 min were significantly lower in the test group than in the placebo group (-0.246 log ng/10 ml [95 % CI -0.395 to -0.098], P = 0.002; -0.349 log ng/10 ml; 95 % CI -0.506 to -0.192; P oxidase has suppressive effects on oral malodor. This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (number: UMIN000015140 , date of registration: 16/09/2014).

Melatonin for chronic whiplash syndrome with delayed melatonin onset randomised, placebo-controlled trial

NARCIS (Netherlands)

Wieringen, S. van; Jansen, T.; Smits, M.G.; Nagtegaal, J.E.; Coenen, A.M.L.

2001-01-01

Objective: To assess the influence of melatonin in patients with chronic whiplash syndrome and delayed melatonin onset. Design: Randomised, double-blind, placebo-controlled, parallel-group trial. One-week baseline was followed by a 4-week treatment period with either melatonin or placebo. In the

Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

Directory of Open Access Journals (Sweden)

Kupchak Brian R

2009-07-01

Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

Effects of a Worksite Weight-Control Programme in Obese Male Workers: A Randomized Controlled Crossover Trial

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Iriyama, Yae; Murayama, Nobuko

2014-01-01

Objective: We conducted a randomized controlled crossover trial to evaluate the effects of a new worksite weight-control programme designed for men with or at risk of obesity using a combination of nutrition education and nutrition environmental interventions. Subjects and methods: Male workers with or at risk of obesity were recruited for this…

PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

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Day Richard O

2010-07-01

Full Text Available Abstract Background Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN for recovery from acute LBP. Methods/Design The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol, PRN paracetamol (plus placebo time-contingent paracetamol or a double placebo study arm. The primary outcome will be time (days to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives. Discussion The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP. Trail registration ACTRN12609000966291.

Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial.

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Micka, Antje; Siepelmeyer, Anne; Holz, Anja; Theis, Stephan; Schön, Christiane

2017-02-01

Constipation is among the most common health impairments in Western countries. This study aimed to determine the effect of the chicory-derived fermentable dietary fiber Orafti ® Inulin on stool frequency in healthy subjects with constipation. The study was conducted according to recent guidance documents for investigating bowel function and used a randomized, double-blind, placebo-controlled, cross-over design with a 2-week wash-out phase. Each study period comprised a run-in phase followed by 4 weeks daily intake of 3 × 4g inulin or maltodextrin (placebo). Forty-four healthy volunteers with constipation documented stool frequency and consistency, gastrointestinal characteristics and quality of life. Consumption of Orafti ® Inulin significantly increased stool frequency compared to placebo (median 4.0 [IQR 2.5-4.5] versus 3.0 [IQR 2.5-4.0] stools/week, p = 0.038). This was accompanied by a softening of stools and trend toward higher satisfaction versus placebo (p = 0.059). In conclusion, Orafti ® Inulin was effective in volunteers with chronic constipation and significantly improved bowel function. This trial was registered at clinicaltrials.gov as NCT02548247.

Antihyperalgesic efficacy of 5% lidocaine medicated plaster in capsaicin and sunburn pain models--two randomized, double-blinded, placebo-controlled crossover trials in healthy volunteers.

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Gustorff, Burkhard; Hauer, David; Thaler, Johannes; Seis, Astrid; Draxler, Julia

2011-12-01

The aim of this research is to analyze analgesic efficacy of the 5% lidocaine medicated plaster in two randomized, double-blinded, placebo-controlled, crossover studies in 16 healthy volunteers using capsaicin and sunburn pain models. Lidocaine and placebo plasters were simultaneously applied to forearms and thighs at contralateral body sites for three alternating 12-h plaster-on/plaster-off periods. Between the second and third plaster-on period, 4.2-cm circular spots on both pretreated thighs were irradiated with three times the individual minimal erythema dose of UVB light. After the last plaster-on period, 20 μl of 0.1% capsaicin was injected intradermally into both forearms. The study was repeated using a single 12-h plaster application. The area of pinprick hyperalgesia was diminished by 53% (p sunburn model; the intensity of mechanical hyperalgesia to rigid filaments (8 - 512 mN) was reduced in both models. Cold pain perception threshold was reduced (19.7°C ± 8.0 vs 21.8°C ± 6.8 for placebo, p sunburn). Similar effects were observed in the 12-h exposure study. No effect was seen on capsaicin-induced spontaneous pain and flare size, or blood flow in the sunburn area, and heat hyperalgesia in either study. Lidocaine plaster effectively treats mechanical hyperalgesia and cold pain.

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

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Jay K Udani

2013-01-01

Full Text Available Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35–65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P<0.05. When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P<0.05. There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

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Udani, Jay K

2013-01-01

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35-65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a single-dose, investigator-blinded, placebo-controlled, crossover trial.

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Wolz, Martin; Schleiffer, Christine; Klingelhöfer, Lisa; Schneider, Christine; Proft, Florian; Schwanebeck, Uta; Reichmann, Heinz; Riederer, Peter; Storch, Alexander

2012-11-01

A previous questionnaire study suggests an increased chocolate consumption in Parkinson's disease (PD). The cacao ingredient contains caffeine analogues and biogenic amines, such as β-phenylethylamine, with assumed antiparkinsonian effects. We thus tested the effects of 200 g of chocolate containing 80 % of cacao on UPDRS motor score after 1 and 3 h in 26 subjects with moderate non-fluctuating PD in a mono-center, single-dose, investigator-blinded crossover study using cacao-free white chocolate as placebo comparator. At 1 h after chocolate intake, mean UPDRS motor scores were mildly decreased compared to baseline in both treatments with significant results only for dark chocolate [-1.3 (95 % CI 0.18-2.52, RMANOVA F = 4.783, p = 0.013¸ Bonferroni p = 0.021 for 1 h values)]. A 2 × 2-cross-over analysis revealed no significant differences between both treatments [-0.54 ± 0.47 (95 % CI -1.50 to 0.42), p = 0.258]. Similar results were obtained at 3 h after intake. β-phenylethylamine blood levels were unaltered. Together, chocolate did not show significant improvement over white cacao-free chocolate in PD motor function.

Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication.

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Momsen, A H; Jensen, M B; Norager, C B; Madsen, M R; Vestersgaard-Andersen, T; Lindholt, J S

2010-10-01

Intermittent claudication is a disabling symptom of peripheral arterial disease for which few medical treatments are available. This study investigated the effect of caffeine on physical capacity in patients with intermittent claudication. This randomized double-blind placebo-controlled crossover study included 88 patients recruited by surgeons from outpatient clinics. The participants abstained from caffeine for 48 h before each test and then received either a placebo or oral caffeine (6 mg/kg). After 75 min, pain-free and maximal walking distance on a treadmill, perceived pain, reaction times, postural stability, maximal isometric knee extension strength, submaximal knee extension endurance and cognitive function were measured. The analysis was by intention to treat. Caffeine increased the pain-free walking distance by 20.0 (95 per cent confidence interval 3.7 to 38.8) per cent (P = 0.014), maximal walking distance by 26.6 (12.1 to 43.0) per cent (P postural stability was reduced significantly, by 22.1 (11.7 to 33.4) per cent with eyes open (P < 0.001) and by 21.8 (7.6 to 37.8) per cent with eyes closed (P = 0.002). Neither reaction time nor cognition was affected. In patients with moderate intermittent claudication, caffeine increased walking distance, maximal strength and endurance, but affected balance adversely.

Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study.

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Erlendson, Matthew J; D'Arcy, Nicole; Encisco, Ellen M; Yu, Jeffrey J; Rincon-Cruz, Lorena; Peltz, Gary; Clark, J David; Chu, Larry F

2017-01-01

Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. At timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Comparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5 ± 0.97; and palonosetron with hydroxyzine, 0.2 ± 0.1333. Pretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal.

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials.

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Chen, Xi; Zou, Kun; Abdullah, Natasya; Whiteside, Nicola; Sarmanova, Aliya; Doherty, Michael; Zhang, Weiya

2017-07-01

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

Veterinary homeopathy: meta-analysis of randomised placebo-controlled trials.

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Mathie, Robert T; Clausen, Jürgen

2015-01-01

Meta-analysis of randomised controlled trials (RCTs) of veterinary homeopathy has not previously been undertaken. For all medical conditions and species collectively, we tested the hypothesis that the outcome of homeopathic intervention (treatment and/or prophylaxis, individualised and/or non-individualised) is distinguishable from corresponding intervention using placebos. All facets of the review, including literature search strategy, study eligibility, data extraction and assessment of risk of bias, were described in an earlier paper. A trial was judged to comprise reliable evidence if its risk of bias was low or was unclear in specific domains of assessment. Effect size was reported as odds ratio (OR). A trial was judged free of vested interest if it was not funded by a homeopathic pharmacy. Meta-analysis was conducted using the random-effects model, with hypothesis-driven sensitivity analysis based on risk of bias. Nine of 15 trials with extractable data displayed high risk of bias; low or unclear risk of bias was attributed to each of the remaining six trials, only two of which comprised reliable evidence without overt vested interest. For all N = 15 trials, pooled OR = 1.69 [95% confidence interval (CI), 1.12 to 2.56]; P = 0.01. For the N = 2 trials with suitably reliable evidence, pooled OR = 2.62 [95% CI, 1.13 to 6.05]; P = 0.02). Meta-analysis provides some very limited evidence that clinical intervention in animals using homeopathic medicines is distinguishable from corresponding intervention using placebos. The low number and quality of the trials hinders a more decisive conclusion. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized, double-blind, placebo-controlled crossover trial.

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Solis, Marina Yazigi; Hayashi, Ana Paula; Artioli, Guilherme Giannini; Roschel, Hamilton; Sapienza, Marcelo Tatit; Otaduy, Maria Concepción; De Sã Pinto, Ana Lucia; Silva, Clovis Artur; Sallum, Adriana Maluf Elias; Pereira, Rosa Maria R; Gualano, Bruno

2016-01-01

It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. © 2015 Wiley Periodicals, Inc.

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study

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Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podg?rski, Tomasz

2017-01-01

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, whil...

Effect of beetroot juice on lowering blood pressure in free-living, disease-free adults: a randomized, placebo-controlled trial

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Coles Leah T

2012-12-01

Full Text Available Abstract Background The consumption of beetroot juice on a low nitrate diet may lower blood pressure (BP and therefore reduce the risk of cardiovascular events. However, it is unknown if its inclusion as part of a normal diet has a similar effect on BP. The aim of the study was to conduct a randomized controlled trial with free-living adults to investigate if consuming beetroot juice in addition to a normal diet produces a measureable reduction in BP. Method Fifteen women and fifteen men participated in a double-blind, randomized, placebo-controlled, crossover study. Volunteers were randomized to receive 500 g of beetroot and apple juice (BJ or a placebo juice (PL. Volunteers had BP measured at baseline and at least hourly for 24-h following juice consumption using an ambulatory blood pressure monitor (ABPM. Volunteers remained at the clinic for 1-h before resuming normal non-strenuous daily activities. The identical procedure was repeated 2-wk later with the drink (BJ or PL not consumed on the first visit. Results Overall, there was a trend (P=0.064 to lower systolic blood pressure (SBP at 6-h after drinking BJ relative to PL. Analysis in men only (n=13 after adjustment for baseline differences demonstrated a significant (P Conclusions Beetroot juice will lower BP in men when consumed as part of a normal diet in free-living healthy adults. Trial registration anzctr.org.au ACTRN12612000445875

A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

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Vance L Albaugh

Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026.

Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial

NARCIS (Netherlands)

Beuers, U.; Spengler, U.; Kruis, W.; AYDEMIR, U.; WIEBECKE, B.; HELDWEIN, W.; WEINZIERL, M.; Pape, G. R.; Sauerbruch, T.; Paumgartner, G.

1992-01-01

The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver

Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial

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Munasinghe, Sujeeva A.; Oliff, Carolyn; Finn, Judith; Wray, John A.

2010-01-01

To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating…

Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial

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R. J. Kuppens

2016-11-01

Full Text Available Abstract Background Patients with Prader-Willi syndrome (PWS have a cognitive impairment. Growth hormone (GH treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Method Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m2/day, both during 1 year. Results Total (TIQ, verbal (VIQ and performance IQ (PIQ did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322. Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Conclusions Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. Trial registration ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

A randomized, double-blind, crossover, placebo-controlled trial of 6 weeks benfotiamine treatment on postprandial vascular function and variables of autonomic nerve function in Type 2 diabetes.

Science.gov (United States)

Stirban, A; Pop, A; Tschoepe, D

2013-10-01

In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population. In a double-blind, placebo-controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal. Participants had an impaired baseline flow-mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow-mediated dilatation, following placebo treatment there was a significant postprandial flow-mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment. In people with Type 2 diabetes and markedly impaired fasting flow-mediated dilatation, a mixed test meal does not further deteriorate flow-mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow-mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Does granisetron eliminate the gag reflex? A crossover, double-blind, placebo-controlled pilot study.

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Barenboim, Silvina Friedlander; Dvoyris, Vladislav; Kaufman, Eliezer

2009-01-01

Although gagging is a frequent problem that, when severe, can jeopardize the dental procedure, no single protocol is used to alleviate this phenomenon. Selective 5-HT3 antagonists, such as granisetron, may attenuate gagging. In this study, granisetron and placebo were administered intravenously, in a crossover, double-blind manner, to 25 healthy volunteers in 2 different sessions. Gagging levels were recorded before and after administration, as were BP, pulse, and O2 saturation. Recorded results were analyzed with the use of tests for nonparametric values (P = .05). A significant increase in the depth of swab insertion was noted after administration of both placebo and drug. The increase in drug effectiveness correlated with decreased body weight. The true efficacy of granisetron in gagger patients with this treatment protocol has yet to be fully established, although it has been theorized that an increased dosage of granisetron may have a better effect.

Blueberry effects on dark vision and recovery after photobleaching: placebo-controlled crossover studies.

Science.gov (United States)

Kalt, Wilhelmina; McDonald, Jane E; Fillmore, Sherry A E; Tremblay, Francois

2014-11-19

Clinical evidence for anthocyanin benefits in night vision is controversial. This paper presents two human trials investigating blueberry anthocyanin effects on dark adaptation, functional night vision, and vision recovery after retinal photobleaching. One trial, S2 (n = 72), employed a 3 week intervention and a 3 week washout, two anthocyanin doses (271 and 7.11 mg cyanidin 3-glucoside equivalents (C3g eq)), and placebo. The other trial, L1 (n = 59), employed a 12 week intervention and an 8 week washout and tested one dose (346 mg C3g eq) and placebo. In both S2 and L1 neither dark adaptation nor night vision was improved by anthocyanin intake. However, in both trials anthocyanin consumption hastened the recovery of visual acuity after photobleaching. In S2 both anthocyanin doses were effective (P = 0.014), and in L1 recovery was improved at 8 weeks (P = 0.027) and 12 weeks (P = 0.030). Although photobleaching recovery was hastened by anthocyanins, it is not known whether this improvement would have an impact on everyday vision.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

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Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

2011-01-01

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

Directory of Open Access Journals (Sweden)

Sara Llufriu

Full Text Available Uncontrolled studies of mesenchymal stem cells (MSCs in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL on magnetic resonance imaging (MRI at 6 months and at the end of the study.Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS 3.0-6.5 were randomized to receive IV 1-2×10(6 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite, and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.At baseline 9 patients were randomized to receive MSCs (n = 5 or placebo (n = 4. One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064, and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075. No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+ cells in blood of MSCs treated patients.Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.

Rates of cognitive change in Alzheimer disease: Observations across a decade of placebo-controlled clinical trials with donepezil

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Jones, Roy W; Schwam, Elias; Wilkinson, David

2009-01-01

Treatment success in Alzheimer disease (AD) trials is generally based on benefits over placebo-treated controls. Consequently, variation in rates of decline among placebo-treated patients could impact outcomes from AD trials. In the present analyses, individual patient data [baseline Mini......-Mental State Examination (MMSE): 10 to 26] were pooled from randomized, placebo-controlled studies of donepezil for AD conducted during the 1990s, and grouped by initiation year-group 1: 1990 to 1994; group 2: 1996 to 1999. Changes in MMSE and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS...

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.

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Dalai, Shebani Sethi; Adler, Sarah; Najarian, Thomas; Safer, Debra Lynn

2018-01-01

Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN. Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood. To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design. Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824. Copyright © 2017 Elsevier Inc. All rights reserved.

A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial.

Directory of Open Access Journals (Sweden)

Clive Ballard

2008-04-01

Full Text Available BACKGROUND: There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. METHODS AND FINDINGS: DESIGN: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. SETTING: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. PARTICIPANTS: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. INTERVENTIONS: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. OUTCOME MEASURES: Primary outcome was total Severe Impairment Battery (SIB score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI. RESULTS: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment, of whom 128 (78% commenced treatment (64 continue/64 placebo. Of those, 26 were lost to follow-up (13 per arm, resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo -0.4 (95% confidence interval [CI] -6.4 to 5.5, adjusted for baseline value (p = 0.9. For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment -2.4 (95% CI -8.2 to 3.5, adjusted for

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

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Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

2014-03-01

Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.

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Wejse, Christian; Gomes, Victor F; Rabna, Paulo; Gustafson, Per; Aaby, Peter; Lisse, Ida M; Andersen, Paul L; Glerup, Henning; Sodemann, Morten

2009-05-01

Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos.

Directory of Open Access Journals (Sweden)

Felicity L Bishop

Full Text Available Placebo groups are used in randomised clinical trials (RCTs to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects.We conducted a content analysis of 45 Participant Information Leaflets (PILs using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database. Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%, but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50:50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001 and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001 or adverse effects (4 vs. 39, p<001. 8 PILs (18% explicitly stated that the placebo treatment was either undesirable or ineffective.PILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

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Amaro, Cynthia M; Bello, Jose A; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson

2018-05-01

To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. ClinicalTrials.gov: NCT01751724. Copyright © 2018 Elsevier Inc. All rights reserved.

EFFICACY OF HYOSCINE BUTYLBROMIDE IN TREATMENT OF IRRITABLE BOWEL SYNDROME IN CHILDREN: PLACEBO-CONTROLLED TRIAL

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K.V. Arifullina

2008-01-01

Full Text Available The activity of hyoscine butylbromide (buscopan was evaluated in a placebobcontrolled trial, on pediatric patients with algid type of irritable bowel syndrome. Hyoscine butylbromide favored to the increase of quality of life in pediatric patients, alleviation of clinical symptoms of disease, reliable decrease of malonic dialdehyde and increase of antioxidant activity of blood plasma significantly superior to placebo. Clinical efficacy of hyoscine butylbromide accompanies to its good tolerance and safety.Key words: children, irritable bowel syndrome, hyoscine butylbromide, placebo controlled trial.

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

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Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

2011-04-01

The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that

The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis

Directory of Open Access Journals (Sweden)

Walach Harald

2005-08-01

Full Text Available Abstract Background and purpose Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. Methods We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. Results We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p Conclusion Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated.

A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness.

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Golier, Julia A; Caramanica, Kimberly; Michaelides, Andreas C; Makotkine, Iouri; Schmeidler, James; Harvey, Philip D; Yehuda, Rachel

2016-02-01

No pharmacological treatments have been demonstrated to effectively treat chronic multisymptom illness (CMI) in Gulf War veterans (GWV). This study assessed the effect of the glucocorticoid receptor antagonist mifepristone in GWV with CMI. A randomized, double-blind, cross-over trial of mifepristone, with two six-week treatment phases separated by a one-month washout period, was conducted at a Veterans Affairs (VA) hospital between 2008 and 2011. Participants were randomized to receive either 200mg of mifepristone per day or matched placebo first. The primary clinical outcome measure was change in self-reported physical health. Neurocognitive functioning and self-reported measures of depression, PTSD, and fatigue were secondary outcomes. Sixty-five participants enrolled, of whom 36 were randomized and 32 (mean age, 49.1 (7.2) years) completed the study. Physical and mental health status and neurocognitive functioning were poor at baseline. Mifepristone treatment was not associated with improvement in self-reported physical health (p=0.838) or in other self-reported measures of mental health. Mifepristone treatment was significantly associated with improvements in verbal learning (p=0.008, d=0.508), in the absence of improvement in other cognitive measures (working memory (p=0.914), visual learning (p=0.643) and a global composite measure (p=0.937). Baseline morning cortisol levels and lysozyme IC50-DEX, a measure of peripheral glucocorticoid sensitivity, displayed a significant relationship with endpoint verbal learning scores (p=0.012 and p=0.007, respectively). The magnitude of cortisol change during treatment mediated the improvement in verbal learning. This study was negative for the primary and secondary clinical outcomes. However, the data suggest a moderate dose of mifepristone may have circumscribed cognitive-enhancing effects in CMI. Further study is warranted to determine whether and through which mechanisms mifepristone treatment can yield clinically

Duloxetine in the treatment of binge eating disorder with depressive disorders: a placebo-controlled trial.

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Guerdjikova, Anna I; McElroy, Susan L; Winstanley, Erin L; Nelson, Eric B; Mori, Nicole; McCoy, Jessica; Keck, Paul E; Hudson, James I

2012-03-01

This study evaluated duloxetine in the treatment of binge eating disorder (BED) with comorbid current depressive disorders. In this 12-week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current depressive disorder received duloxetine (N = 20) or placebo (N = 20). The primary outcome measure was weekly binge eating day frequency. In the primary analysis, duloxetine (mean 78.7 mg/day) was superior to placebo in reducing weekly frequency of binge eating days (p = .04), binge eating episodes (p = .02), weight (p = .04), and Clinical Global Impression-Severity of Illness ratings for binge eating (p = .02) and depressive disorders (p = .01). Changes in body mass index and measures of eating pathology, depression, and anxiety did not differ between the two groups. Duloxetine may be effective for reducing binge eating, weight, and global severity of illness in BED with a comorbid current depressive disorder, but this finding needs confirmation in larger, placebo-controlled trials. Copyright © 2011 Wiley Periodicals, Inc.

Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: A randomized, double-blind crossover trial

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Bogaard, Bas; Draijer, Richard; Westerhof, Berend; Meiracker, Anton; Montfrans, Gert; Born, B.J.H.

2010-01-01

textabstractFlavanol-rich cocoa products have been reported to lower blood pressure. It has been suggested that theobromine is partially responsible for this effect. We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure. In a double-blind, placebo-controlled 3-period crossover trial we assigned 42 healthy individuals (age 62±4.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg...

Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study.

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Anton, Stephen D; Shuster, Jonathan; Leeuwenburgh, Christiaan

2011-11-01

Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is hydroxycitric acid (HCA) derived from Garcinia cambogia Desr. The objective of this article is to describe the protocol of a clinical trial designed to directly test the effects of Garcinia cambogia-derived HCA on food intake, satiety, weight loss and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight or obese individuals (with a body mass index range of 25.0 to 39.9 kg/m(2)) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day. This study can be completed with far fewer subjects than a parallel design. Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA is selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial. ClinicalTrials.gov (Identifier: NCT01238887).

Effect of fibular repositioning taping in adult basketball players with chronic ankle instability: a randomized, placebo-controlled, crossover trial.

Science.gov (United States)

Alves, Yanina; Ribeiro, Fernando; Silva, Anabela G

2017-07-05

Chronic ankle instability presents a high incidence and prevalence in basketbal players. It's important to develop strategies to reduce the functional and mechanical limitations resulting from this condition. To compare the effect of Mulligan ́s fibular repositioning taping with a placebo taping immediatly after application and after a running test (Yo-Yo IRT). 16 adult basketball players (10 male, 6 female) with chronic ankle instability and mean age 21.50 ± 2.76 years old. Assessment of static postural control (15 seconds of unipedal stance test with eyes closed in a force platform), functional performance (figure 8 hop test and lateral hop test) and neuromuscular control (peroneus longus latency time in sudden inversion) in two conditions: Mulligan and Placebo. No significant effect was found for the intervantion factor in both hop tests (p>0.170), but there was a significant effect for the time factor (p<0.03). For the peroneus longus latency time, there was a significant interaction between factors (p=0.028) and also for time (p=0.042). No significant effect was found for any of the static postural control variables (area, speed and total displacement) (p≥0.10). There was no differences between Mulligan's fibular repositioning taping and Placebo taping in postural control and functional performance in basketball players with chronic ankle instability. However, Mulligan's taping appears to reduce peroneus longus latency time after a running when compared with a placebo taping.

Effect of Persian Medicine Remedy on Chemotherapy Induced Nausea and Vomiting in Breast Cancer: A Double Blind, Randomized, Crossover Clinical Trial

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Nazari, Mohammad; Taghizadeh, Ali; Bazzaz, Mojtaba Mousavi; Rakhshandeh, Hassan; Shokri, Sadegh

2017-01-01

Background Chemotherapy induced nausea and vomiting (CINV) is a side effect, and has negative effect on quality of life and continuation of chemotherapy. Despite new regimen and drugs, the problems still remain and standard guidelines, effective treatment and supportive care for refractory CINV are still not yet established. Persian medicine, the old Iranian medical school, offer Persumac (prepared from Rhus Coriaria and Bunium Persicum Boiss). Objective The specific objectives were to assess the effect of Persumac on the number and severity of nausea and vomiting in refractory CINV in acute and delayed phase. Methods This randomized, double blind, crossover clinical trial study was carried out on 93 patients with breast cancer and refractory CINV, who received outpatient high emetogenic chemotherapy in Imam Reza hospital, Mashhad, Iran from October 2015 to May 2016. The study has three stages: in stage I patients received a questionaire and completed it after chemotherapy. In stage II they were randomly divided into intervention group with Persumac and control group with placebo (lactose were used). In stage III, wash out and crossover was conducted. Both groups in all stages received standard antiemetic therapy for CINV. The following were set as the inclusion criteria of the study: female, Age ≥18 years, clinical diagnosis of breast cancer, history of refractory CINV, normal blood tests and at least three courses of chemotherapy remaining. Exclusion criteria of this study were: Total or upper abdominal radiation therapy along with chemotherapy, drugs/therapy for nausea and vomiting not prescribed in this study, hypersensitivity to Sumac or Bunium Persicum, use of sumac and Bunium Persicum in seven days prior to the intervention, clinical diagnosis of digestion disorders, non-chemotherapy induced nausea and vomiting, milk allergy, loss of two consecutive or three intermittent doses of Persumac or placebo. Outcomes were gathered by Persian questionnaire. Number

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

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Dietlind L. Wahner-Roedler

2011-01-01

Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

OpenAIRE

Little, A; Levy, R; Chuaqui-Kidd, P; Hand, D

1985-01-01

The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improve...

Escitalopram in the Treatment of Adolescent Depression: A Randomized Placebo-Controlled Multisite Trial

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Emslie, Graham J.; Ventura, Daniel; Korotzer, Andrew; Tourkodimitris, Stavros

2009-01-01

A randomized, double-blind, placebo-controlled trial that involves 312 male and female patients aged 12-17 reveal the effectiveness of escitalopram in the treatment of depressed adolescents. Eighty-three percent of the participants or 259 participants completed the 8 weeks therapy period.

Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial.

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Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle

2018-01-01

Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

Science.gov (United States)

Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

International Nuclear Information System (INIS)

Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

2011-01-01

Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis

Effects of carbohydrates-BCAAs-caffeine ingestion on performance and neuromuscular function during a 2-h treadmill run: a randomized, double-blind, cross-over placebo-controlled study

Directory of Open Access Journals (Sweden)

Peltier Sébastien L

2011-12-01

Full Text Available Abstract Background Carbohydrates (CHOs, branched-chain amino acids (BCAAs and caffeine are known to improve running performance. However, no information is available on the effects of a combination of these ingredients on performance and neuromuscular function during running. Methods The present study was designed as a randomized double-blind cross-over placebo-controlled trial. Thirteen trained adult males completed two protocols, each including two conditions: placebo (PLA and Sports Drink (SPD: CHOs 68.6 g.L-1, BCAAs 4 g.L-1, caffeine 75 mg.L-1. Protocol 1 consisted of an all-out 2 h treadmill run. Total distance run and glycemia were measured. In protocol 2, subjects exercised for 2 h at 95% of their lowest average speeds recorded during protocol 1 (whatever the condition. Glycemia, blood lactate concentration and neuromuscular function were determined immediately before and after exercise. Oxygen consumption (V˙O2, heart rate (HR and rate of perceived exertion (RPE were recorded during the exercise. Total fluids ingested were 2 L whatever the protocols and conditions. Results Compared to PLA, ingestion of SPD increased running performance (p = 0.01, maintained glycemia and attenuated central fatigue (p = 0.04, an index of peripheral fatigue (p = 0.04 and RPE (p = 0.006. Maximal voluntary contraction, V˙O2, and HR did not differ between the two conditions. Conclusions This study showed that ingestion of a combination of CHOs, BCAAs and caffeine increased performance by about 2% during a 2-h treadmill run. The results of neuromuscular function were contrasted: no clear cut effects of SPD were observed. Trial registration ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00799630

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

Science.gov (United States)

Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podgórski, Tomasz

2017-07-14

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased ( p = 0.049) with a simultaneous reduction of fat mass ( p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold ( p athletes.

Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma.

Science.gov (United States)

Wong, Eliza L Y; Sung, Rita Yn Tz; Leung, Ting Fan; Wong, Yeuk Oi; Li, Albert M C; Cheung, Kam Lau; Wong, Chun Kwok; Fok, Tai Fai; Leung, Ping Chung

2009-10-01

The purpose of this trial was to evaluate whether the herbal formula of CUF2 used as complementary therapy improves the clinical symptoms and biochemical markers in children with asthma using inhaled corticosteroids. In a double-blind, placebo-controlled prospective trial, 85 children with asthma aged 7-15 years were randomly assigned to receive either a daily oral herbal formula of 0.619-g CUF2 capsule of dried aqueous extract with an equal weight of five herbs (Astragalus mongholius Bunge, Cordyceps sinensis Sacc., Radix stemonae, Bulbus fritillariae cirrhosae, and Radix scutellariae) or placebo for 6 months. The primary endpoint was the change in steroids dosage; the secondary outcomes included the disease severity score, lung function test, and biochemical markers in blood. Eighty-five (85) children (42 on active treatment and 43 on placebo) completed the 6-month clinical trial. Children randomized to the herbal formula of CUF2 and the placebo showed a similar improvement in clinical symptoms and biomedical markers. The comparison between the CUF2 group and the placebo group showed no significant difference on the dosage of steroids (-2.3 versus -3.1 mg, p = 0.915), disease severity score (-2.3 versus -3.1, p = 0.215), and lung function test of forced expiratory volume in 1 second/forced vital capacity percent (0.1 versus 0.6%, p = 0.809) and peak expiratory flow rate (-7.3 versus -0.6 l/minutes, p = 0.118). No significant difference was found between the two study groups in the biochemical outcomes measured. The intervention effect of CUF2 was smaller than the placebo effect. This study provides no evidence to support the use of the herbal formula of CUF2 in children with asthma. Parents are thus advised to discuss with health professionals before choosing an herbal formula in preference to conventional treatment modes.

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

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Berk Michael

2012-08-01

Full Text Available Abstract Background N-acetyl cysteine (NAC is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149 had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493.

Tranexamic Acid for Lower GI Hemorrhage: A Randomized Placebo-Controlled Clinical Trial.

Science.gov (United States)

Smith, Stephen R; Murray, David; Pockney, Peter G; Bendinelli, Cino; Draganic, Brian D; Carroll, Rosemary

2018-01-01

Lower GI hemorrhage is a common source of morbidity and mortality. Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss in a variety of clinical conditions. Information regarding the use of tranexamic acid in treating lower GI hemorrhage is lacking. The aim of this trial was to determine the clinical efficacy of tranexamic acid when used for lower GI hemorrhage. This was a prospective, double-blind, placebo-controlled, randomized clinical trial. The study was conducted at a tertiary referral university hospital in Australia. Consecutive patients aged >18 years with lower GI hemorrhage requiring hospital admission from November 2011 to January 2014 were screened for trial eligibility (N = 265). A total of 100 patients were recruited after exclusions and were randomly assigned 1:1 to either tranexamic acid or placebo. The primary outcome was blood loss as determined by reduction in hemoglobin levels. The secondary outcomes were transfusion rates, transfusion volume, intervention rates for bleeding, length of hospital stay, readmission, and complication rates. There was no difference between groups with respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p = 0.9445). There was no difference with respect to transfusion rates (14/49 tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs 1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No complications occurred as a direct result of tranexamic acid use. A larger multicenter trial may be required to determine whether there are more subtle advantages with tranexamic acid use in some of the secondary outcomes. Tranexamic acid does not appear to decrease blood loss or improve clinical outcomes in patients presenting with lower GI hemorrhage in the context of this trial. see Video Abstract at http://links.lww.com/DCR/A453.

Effect of aromatherapy massage on menopausal symptoms: a randomized placebo-controlled clinical trial.

Science.gov (United States)

Darsareh, Fatemeh; Taavoni, Simin; Joolaee, Soodabeh; Haghani, Hamid

2012-09-01

Menopause is a significant event in most women's lives because it marks the end of a woman's natural reproductive life. The purpose of this study was to determine the effect of aromatherapy massage on menopausal symptoms. A randomized placebo-controlled clinical trial was conducted at a menopausal clinic at a gynecology hospital in Tehran. The study population comprised 90 women who were assigned to an aromatherapy massage group, a placebo massage group, or a control group. Each participant in the aromatherapy massage group received 30-minute aromatherapy treatment sessions twice a week for 4 weeks with aroma oil, whereas participants in the placebo massage group received the same treatment with plain oil. No treatment was provided to participants in the control group. The outcome measures in this study were menopausal symptoms, as obtained through the Menopause Rating Scale. The mean baseline level of the menopausal score did not differ among all groups. However, after eight sessions of intervention, the Menopause Rating Scale score differed significantly among the three groups (P aromatherapy massage group and the placebo massage group had a lower menopausal score than the control group (P aromatherapy massage and the placebo massage groups were compared, the menopausal score for the aromatherapy massage group was found to be significantly lower (P aromatherapy massage were effective in reducing menopausal symptoms. However, aromatherapy massage was more effective than only massage.

Bell's Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial.

Science.gov (United States)

Babl, Franz E; Mackay, Mark T; Borland, Meredith L; Herd, David W; Kochar, Amit; Hort, Jason; Rao, Arjun; Cheek, John A; Furyk, Jeremy; Barrow, Lisa; George, Shane; Zhang, Michael; Gardiner, Kaya; Lee, Katherine J; Davidson, Andrew; Berkowitz, Robert; Sullivan, Frank; Porrello, Emily; Dalziel, Kim Marie; Anderson, Vicki; Oakley, Ed; Hopper, Sandy; Williams, Fiona; Wilson, Catherine; Williams, Amanda; Dalziel, Stuart R

2017-02-13

Bell's palsy or acute idiopathic lower motor neurone facial paralysis is characterized by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. While there is high level evidence in adults demonstrating an improvement in the rate of complete recovery of facial nerve function when treated with steroids compared with placebo, similar high level studies on the use of steroids in Bell's palsy in children are not available. The aim of this study is to assess the utility of steroids in Bell's palsy in children in a randomised placebo-controlled trial. We are conducting a randomised, triple-blinded, placebo controlled trial of the use of prednisolone to improve recovery from Bell's palsy at 1 month. Study sites are 10 hospitals within the Australian and New Zealand PREDICT (Paediatric Research in Emergency Departments International Collaborative) research network. 540 participants will be enrolled. To be eligible patients need to be aged 6 months to Bell's palsy to one of the participating hospital emergency departments. Patients will be excluded in case of current use of or contraindications to steroids or if there is an alternative diagnosis. Participants will receive either prednisolone 1 mg/kg/day to a maximum of 50 mg/day or taste matched placebo for 10 days. The primary outcome is complete recovery by House-Brackmann scale at 1 month. Secondary outcomes include assessment of recovery using the Sunnybrook scale, the emotional and functional wellbeing of the participants using the Pediatric Quality of Life Inventory and Child Health Utility 9D Scale, pain using Faces Pain Scale Revised or visual analogue scales, synkinesis using a synkinesis assessment questionnaire and health utilisation costs at 1, 3 and 6 months. Participants will be tracked to 12 months if not recovered earlier. Data analysis will be by intention to treat with primary outcome presented as differences in proportions and an odds ratio

Relationship of a Special Acidified Milk Protein Drink with Cognitive Performance: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Young Adults

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Yoshie Saito

2018-05-01

Full Text Available A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchida–Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink. Subjects showed a significant improvement in performance in the Uchida–Kraepelin test, the primary outcome measured, when they consumed the acidified milk protein drink compared with the placebo control condition. In addition, consumption of the acidified milk protein drink, compared with the placebo control, was associated with increases in vagally-mediated heart rate variability indices which, from recent theoretical perspectives, may reflect a higher ability to modulate cognitive and behavioral processes. There was no significant difference in subjective feelings and body temperature between the test drink conditions. These data suggest that consumption of the acidified milk protein drink may improve cognitive performance, with possible involvement of physiological systems that regulate cognition and behavior.

BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

Directory of Open Access Journals (Sweden)

Singh Betsy B

2009-06-01

Full Text Available Abstract Background Delayed onset muscle soreness (DOMS is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise. Methods The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. Results In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein and muscle damage (creatine phosphokinase and myoglobin. Conclusion BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.

BounceBack capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study.

Science.gov (United States)

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-06-05

Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack, to alleviate the severity of DOMS after standardized eccentric exercise. The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18-45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. In this controlled pilot study, intake of BounceBack capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). BounceBack capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.

BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

Science.gov (United States)

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-01-01

Background Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise. Methods The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. Results In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). Conclusion BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results. PMID:19500355

A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

Science.gov (United States)

Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

2012-01-01

Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial

Directory of Open Access Journals (Sweden)

Ahmad Ghanizadeh

2017-04-01

Full Text Available Objective: Glutamate is considered a target for treating obsessive-compulsive disorder (OCD. The efficacy and safety of the nutritional supplement of N-Acetylcysteine (NAC as an adjuvant to serotonin reuptake inhibitor (SSRI for treating children and adolescents with OCD has never been examined.Methods: This was a 10-week randomized double-blind placebo-controlled clinical trial with 34 OCD outpatients. The patients received citalopram plus NAC or placebo. Yale-Brown Obsessive-Compulsive Scale (YBOCS and Pediatric Quality of Life Inventory (PedsQL™ were used. Adverse effects were monitored.Results: YBOCS score was not different between the two groups at baseline, but the score was different between the two groups at the end of this trial (P<0.02. The YBOCS score of NAC group significantly decreased from 21.0(8.2 to 11.3(5.7 during this study. However, no statistically significant decrease of YBOCS was found in the placebo group. The Cohen’s d effect size was 0.83.The mean change of score of resistance/control to obsessions in the NAC and placebo groups was 1.8(2.3 and 0.8(2.1, respectively (P = 0.2. However, the mean score of change for resistance/control to compulsion in the NAC and placebo groups was 2.3(1.8 and 0.9(2.3, respectively. Cohen’s d effect size was 0.42.The score of three domains of quality of life significantly decreased in N-Acetylcysteine group during this trial. However, no statistically significant decrease was detected in the placebo group. No serious adverse effect was found in the two groups.Conclusion: This trial suggests that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents. In addition, it is well tolerated.

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

Science.gov (United States)

Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

2017-10-03

The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

Implant decontamination during surgical peri-implantitis treatment : a randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

de Waal, Yvonne C. M.; Raghoebar, Gerry M.; Huddleston Slater, James J. R.; Meijer, Henny J. A.; Winkel, Edwin G.; van Winkelhoff, Arie Jan

Aim The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. Material & Methods Thirty patients (79 implants) with

Implant decontamination during surgical peri-implantitis treatment : a randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

de Waal, Yvonne C.M.; Raghoebar, Gerry M; Huddleston Slater, James J R; Meijer, Hendrikus; Winkel, Edwin G; van Winkelhoff, Arie Jan

AIM: The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. MATERIAL & METHODS: Thirty patients (79 implants) with

No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study.

Science.gov (United States)

Ludäscher, Petra; Schmahl, Christian; Feldmann, Robert E; Kleindienst, Nikolaus; Schneider, Miriam; Bohus, Martin

2015-10-01

Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder. © The Author(s) 2015.

Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial.

Science.gov (United States)

Kuppens, R J; Mahabier, E F; Bakker, N E; Siemensma, E P C; Donze, S H; Hokken-Koelega, A C S

2016-11-16

Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m 2 /day), both during 1 year. Total (TIQ), verbal (VIQ) and performance IQ (PIQ) did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322). Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

The effect of dipeptidyl peptidase 4 inhibition on gastric volume, satiation and enteroendocrine secretion in Type 2 diabetes: a double blind, placebo-controlled crossover study

DEFF Research Database (Denmark)

Vella, Adrian; Bock, Gerlies; Giesler, Paula D

2008-01-01

with type 2 diabetes. Methods: In a double blind, placebo-controlled crossover design, 14 subjects with type 2 diabetes received vildagliptin (50mg bid) or placebo for 10-days in random order separated by a 2-week washout. On day 7, fasting and post-meal gastric volumes were measured by a (99m...... ingested was recorded and symptoms similarly measured using VAS. Results: Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 + 21 vs. 247 + 19ml, p= 0.98) and fed (746 + 28 vs. 772 + 26ml, p= 0.54) gastric volumes, did not differ when subjects received vildagliptin or placebo. Treatment...... with vildagliptin did not alter the maximum tolerated volume of Ensure((R)) (1657 + 308 vs. 1389 + 197 ml, p= 0.15) or water compared to placebo (1371 + 141 vs. 1172 + 156 ml, p= 0.23). Vildagliptin was associated with decreased PYY concentrations 60 minutes after initiation of the meal (166 +/- 27 vs. 229 +/- 34...

Treatment of post-myocardial infarction depressive disorder : A randomized, placebo-controlled trial with mirtazapine

NARCIS (Netherlands)

Honig, Adriaan; Kuyper, Astrid M. G.; Schene, Aart H.; van Melle, Joost P.; De Jonge, Peter; Tulner, Dorien M.; Schins, Annique; Crijns, Harry J. G. M.; Kuijpers, Petra M. J. C.; Vossen, Helen; Lousberg, Richel; Ormel, Johan

Objective: To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective

Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

Science.gov (United States)

Talley, N J; Tack, J; Ptak, T; Gupta, R; Giguère, M

2008-06-01

Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.

Design Dilemma: The Debate over Using Placebos in Cancer Clinical Trials

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Many patients and researchers assert that in cancer clinical trials, placebos are inappropriate and that all participants should receive active treatment. But with the emergence of molecularly targeted anticancer agents, some cancer researchers believe placebo-controlled trials are now feasible and, in some cases, necessary.

Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial.

Science.gov (United States)

Kuppens, R J; Donze, S H; Hokken-Koelega, A C S

2016-12-01

Prader-Willi syndrome (PWS) is known for hyperphagia with impaired satiety and a specific behavioural phenotype with stubbornness, temper tantrums, manipulative and controlling behaviour and obsessive-compulsive features. PWS is associated with hypothalamic and oxytocinergic dysfunction. In humans without PWS, intranasal oxytocin administration had positive effects on social and eating behaviour, and weight balance. To evaluate the effects of intranasal oxytocin compared to placebo administration on social behaviour and hyperphagia in children with PWS. Randomized, double-blind, placebo-controlled, crossover study in a PWS Reference Center in the Netherlands. Crossover intervention with twice daily intranasal oxytocin (dose range 24-48 IU/day) and placebo administration, both during 4 weeks, in 25 children with PWS (aged 6 to 14 years). In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found, but in the 17 children younger than 11 years, parents reported significantly less anger (P = 0·001), sadness (P = 0·005), conflicts (P = 0·010) and food-related behaviour (P = 0·011), and improvement of social behaviour (P = 0·018) during oxytocin treatment compared with placebo. In the eight children older than 11 years, the items happiness (P = 0·039), anger (P = 0·042) and sadness (P = 0·042) were negatively influenced by oxytocin treatment compared to placebo. There were no side effects or adverse events. This randomized, double-blind, placebo-controlled study suggests that intranasal oxytocin administration has beneficial effects on social behaviour and food-related behaviour in children with PWS younger than 11 years of age, but not in those older than 11 years of age. © 2016 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram.

Science.gov (United States)

Lavretsky, Helen; Siddarth, Prabha; Irwin, Michael R

2010-02-01

This study examined the potential of an antidepressant drug, escitalopram, to improve depression, resilience to stress, and quality of life in family dementia caregivers in a randomized placebo-controlled double-blinded trial. Forty family caregivers (43-91 years of age, 25 children and 15 spouses; 26 women) who were taking care of their relatives with Alzheimer disease were randomized to receive either escitalopram 10 mg/day or placebo for 12 weeks. Severity of depression, resilience, burden, distress, quality of life, and severity of care-recipient's cognitive and behavioral disturbances were assessed at baseline and over the course of the study. The Hamilton Depression Rating Scale scores at baseline ranged between 10 and 28. The groups were stratified by the diagnosis of major and minor depression. Most outcomes favored escitalopram over placebo. The severity of depression improved, and the remission rate was greater with the drug compared with placebo. Measures of anxiety, resilience, burden, and distress improved on escitalopram compared with placebo. Among caregivers, this small randomized controlled trial found that escitalopram use resulted in improvement in depression, resilience, burden and distress, and quality of life. Our results need to be confirmed in a larger sample.

Effectiveness of low-dose doxycycline (LDD on clinical symptoms of Sjögren's Syndrome: a randomized, double-blind, placebo controlled cross-over study

Directory of Open Access Journals (Sweden)

Vuotila Tuija

2007-12-01

Full Text Available Abstract Background Matrix metalloproteinases (MMPs are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS. Low-dose doxycycline (LDD inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients. This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately. Results Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p Conclusion LDD may not be useful in reducing the primary SS symptoms.

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

Science.gov (United States)

Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

2017-07-01

Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.

Science.gov (United States)

Barnes, Thomas R E; Leeson, Verity C; Paton, Carol; Costelloe, Céire; Simon, Judit; Kiss, Noemi; Osborn, David; Killaspy, Helen; Craig, Tom K J; Lewis, Shôn; Keown, Patrick; Ismail, Shajahan; Crawford, Mike; Baldwin, David; Lewis, Glyn; Geddes, John; Kumar, Manoj; Pathak, Rudresh; Taylor, Simon

2016-04-01

Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. Adult psychiatric services, treating people with schizophrenia. Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week

Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

2017-02-01

Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m 2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

Misoprostol for cervical priming prior to hysteroscopy in postmenopausal and premenopausal nulliparous women; a multicentre randomised placebo controlled trial

NARCIS (Netherlands)

Tasma, M L; Louwerse, M D; Hehenkamp, W J; Geomini, P M; Bongers, M Y; Veersema, S; van Kesteren, P J; Tromp, E; Huirne, J A; Graziosi, G C

OBJECTIVE: To evaluate the reduction of pain by misoprostol compared with placebo prior to hysteroscopy in postmenopausal and premenopausal nulliparous women. DESIGN: Randomised multicentre double-blind placebo controlled trial. SETTING: Two Dutch teaching hospitals and one Dutch university medical

Placebo Response and Practice Effects in Schizophrenia Cognition Trials.

Science.gov (United States)

Keefe, Richard S E; Davis, Vicki G; Harvey, Philip D; Atkins, Alexandra S; Haig, George M; Hagino, Owen; Marder, Stephen; Hilt, Dana C; Umbricht, Daniel

2017-08-01

Patients' previous experience with performance-based cognitive tests in clinical trials for cognitive impairment associated with schizophrenia can create practice-related improvements. Placebo-controlled trials for cognitive impairment associated with schizophrenia are at risk for these practice effects, which can be difficult to distinguish from placebo effects. To conduct a systematic evaluation of the magnitude of practice effects on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) in cognitive impairment associated with schizophrenia and to examine which demographic, clinical, and cognitive characteristics were associated with improvement in placebo conditions. A blinded review was conducted of data from 813 patients with schizophrenia who were treated with placebo in 12 randomized placebo-controlled clinical trials conducted mostly in outpatient clinics in North America, Europe, Asia, and Latin America from February 22, 2007, to March 1, 2014. A total of 779 patients provided data for the primary outcome measure at baseline and at least 1 follow-up. Seven trials had prebaseline assessments wherein the patients knew that they were not receiving treatment, allowing a comparison of practice and placebo effects in the same patients. Placebo compared with various experimental drug treatments. Composite score on the MCCB. Of the 813 patients in the study (260 women and 553 men; mean [SD] age, 41.2 [11.5] years), the mean MCCB composite score at baseline was 22.8 points below the normative mean, and the mean (SEM) total change in the MCCB during receipt of placebo was 1.8 (0.2) T-score points (95% CI, 1.40-2.18), equivalent to a change of 0.18 SD. Practice effects in the 7 studies in which there was a prebaseline assessment were essentially identical to the postbaseline placebo changes. Baseline factors associated with greater improvements in the MCCB during receipt of placebo included more depression

Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy

Science.gov (United States)

Grangé, Gilles; Jacob, Nelly; Tanguy, Marie-Laure

2014-01-01

Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self

Suicide risk in placebo-controlled studies of major depression

NARCIS (Netherlands)

Storosum, J. G.; van Zwieten, B. J.; van den Brink, W.; Gersons, B. P.; Broekmans, A. W.

2001-01-01

The purpose of this study was to determine if fear of an increased risk of attempted suicide in placebo groups participating in placebo-controlled studies is an argument against the performance of placebo-controlled trials in studies of major depression. All short-term and long-term,

Imipramine and Pregabalin Combination for Painful Polyneuropathy. A Randomized Controlled Trial

DEFF Research Database (Denmark)

Holbech, Jakob V; Bach, Flemming W; Finnerup, Nanna B

2015-01-01

Monotherapy with first-line drugs for neuropathic pain often fails to provide sufficient pain relief or has unacceptable side effects because of the need for high doses. The aim of this trial was to test whether the combination of imipramine and pregabalin in moderate doses would relieve pain more...... effectively than monotherapy with either of the drugs. This was a randomized, double-blind, placebo-controlled, crossover, multicenter trial consisting of four 5-week treatment periods in patients with painful polyneuropathy. Treatment arms were imipramine 75 mg/d vs pregabalin 300 mg/d vs combination therapy...... randomized, and 69 patients were included in the data analysis. The effect on average pain in comparison with placebo was: combination (-1.67 NRS points, P pregabalin (-0.48 NRS points, P = 0.03). The combination therapy had significantly lower pain...

Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial.

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Mombelli, Andrea; Almaghlouth, Adnan; Cionca, Norbert; Courvoisier, Delphine S; Giannopoulou, Catherine

2015-03-01

The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 ± 5.2; group B: 2.2 ± 5.0) was not significantly different and was sustained over 12 months in both groups. Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.

Randomised, Double Blind, Placebo-Controlled Trial of Echinacea Supplementation in Air Travellers

Directory of Open Access Journals (Sweden)

E. Tiralongo

2012-01-01

Full Text Available Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P<0.0005. However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P=0.05 during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.

A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption

Directory of Open Access Journals (Sweden)

Kokubo Takeshi

2013-02-01

Full Text Available Abstract Background Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism. Methods This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA, and a profile of mood states (POMS and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase. In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption. Results There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism. Conclusions Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the

A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain.

Science.gov (United States)

Henderson, D C; Fan, X; Copeland, P M; Borba, C P; Daley, T B; Nguyen, D D; Zhang, H; Hayden, D; Freudenreich, O; Cather, C; Evins, A E; Goff, D C

2007-02-01

This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.

Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism.

Science.gov (United States)

Kahaly, George J; Riedl, Michaela; König, Jochem; Diana, Tanja; Schomburg, Lutz

2017-11-01

Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Evaluate efficacy of add-on Se on medical treatment in GD. Double-blind, placebo-controlled, randomized supplementation trial. Academic endocrine outpatient clinic. Seventy untreated hyperthyroid patients with GD. Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo. MMI was discontinued at 24 weeks in euthyroid patients. Response rate (week 24), recurrence rate (week 36), and safety. A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24 [odds ratio (OR) 0.93; 95% confidence interval (CI), 0.26 to 3.25; P = 0.904] in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13; 95% CI, 0.29 to 2.66; P = 0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85; 95% CI, 0.31 to 2.32; P = 0.80). Serum levels of free triiodothyronine/free tetraiodothyronine, thyroid-stimulating hormone receptor antibody, prevalence of moderate to severe Graves orbitopathy, thyroid volume, and MMI starting dose were significantly lower in responders than in nonresponders. A total of 56 and 63 adverse events occurred in the Se and placebo groups, respectively (P = 0.164), whereas only one drug-related side effect (2.9%) was noted in 35 patients on placebo + MMI. Supplemental Se did not affect response or recurrence rates in GD. Copyright © 2017 Endocrine Society

Paracetamol 325 mg/tramadol 37.5 mg effect on pain during needle electromyography: a double-blind crossover clinical trial.

Science.gov (United States)

Kalantar, Seyed Sadeq; Abbasi, Mehrshad; Faghihi-Kashani, Sara; Majedi, Hossein; Ahmadi, Mona; Agah, Elmira; Tafakhori, Abbas

2016-12-01

Needle insertion during electromyography (EMG) may cause varying levels of pain that could lead to inaccurate assessment and premature termination of the procedure. The aim of this study is to compare paracetamol 325 mg/tramadol 37.5 mg with placebo in relieving pain before EMG. This is a randomized, crossover, placebo-controlled, double-blind clinical trial; forty-four healthy individuals, including 27 males with a mean age of 35.3 years (range 18-59 years), entered this study. The needles were inserted unilaterally 2 h after administration of two analgesic tablets of paracetamol 325 mg/tramadol 37.5 mg or two placebo tablets. The pain was scored through a 100-mm visual analog scale (VAS) immediately and 2 h after the procedure. The side effects were also recorded. Within a week, the procedure was repeated on the other upper limb, changing the treatment and placebo. The immediate and 2-h VAS scores were notably lower after administration of treatment compared to placebo (immediate pain: 17.5 ± 12.8 vs. 32.1 ± 16.0, P pain: 1.6 ± 5.6 vs. 5.8 ± 7.9, P = 0. 002). There was a higher prevalence of side effects when treatment was used (48 vs. 9 %, P pain. Further application of this medication in patients with neuromuscular disorders would warrant additional clinical trials, particularly considering the adverse events.

A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

Science.gov (United States)

Kluckow, Martin; Jeffery, Michele; Gill, Andy; Evans, Nick

2014-03-01

Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. Multicentre, double-blind, placebo-controlled randomised trial. Three neonatal intensive care units in Australia. Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. Death or abnormal cranial ultrasound. The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial.

Science.gov (United States)

Ehrhardt, Stephan; Guo, Nan; Hinz, Rebecca; Schoppen, Stefanie; May, Jürgen; Reiser, Markus; Schroeder, Maximilian Philipp; Schmiedel, Stefan; Keuchel, Martin; Reisinger, Emil C; Langeheinecke, Andreas; de Weerth, Andreas; Schuchmann, Marcus; Schaberg, Tom; Ligges, Sandra; Eveslage, Maria; Hagen, Ralf M; Burchard, Gerd D; Lohse, Ansgar W

2016-01-01

Background.  Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Data on the efficacy of probiotics to prevent AAD and CDAD are unclear. We aimed to evaluate the efficacy of Saccharomyces boulardii to prevent AAD and CDAD in hospitalized adult patients. Methods.  We conducted a multicenter, phase III, double-masked, randomized, placebo-controlled trial in hospitalized patients who received systemic antibiotic treatment in 15 hospitals in Germany between July 2010 and October 2012. Participants received Perenterol forte 250 mg capsules or matching placebo twice per day within 24 hours of initiating antibiotic treatment, continued treatment for 7 days after antibiotic discontinuation, and were then observed for 6 weeks. Results.  Two thousand four hundred forty-four patients were screened. The trial was stopped early for futility after inclusion of 477 participants. Two hundred forty-six patients aged 60.1 ± 16.5 years and 231 patients aged 56.5 ± 17.8 were randomized to the S boulardii group and the placebo group, respectively, with 21 and 19 AADs in the respective groups (P = .87). The hazard ratio of AAD in the S boulardii group compared with the placebo group was 1.02 (95% confidence interval, .55-1.90; P = .94). Clostridium difficile-associated diarrhea occurred in 0.8% of participants (4 of 477). Nine serious adverse events were recorded in the S boulardii group, and 3 serious adverse events were recorded in the placebo group. None were related to study participation. Conclusions.  We found no evidence for an effect of S boulardii in preventing AAD or CDAD in a population of hospitalized patients without particular risk factors apart from systemic antibiotic treatment. ClinicalTrials.gov Identifier.  NCT01143272.

Open-label placebo treatment in chronic low back pain: a randomized controlled trial.

Science.gov (United States)

Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J; Kirsch, Irving

2016-12-01

This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (-0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain.

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

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Heinisch, B B; Vila, G; Resl, M; Riedl, M; Dieplinger, B; Mueller, T; Luger, A; Pacini, G; Clodi, M

2012-05-01

B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m(2); fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured. Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. ClinicalTrials.gov: NCT01324739 The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

High-volume infiltration analgesia in total knee arthroplasty: a randomized, double-blind, placebo-controlled trial

DEFF Research Database (Denmark)

Andersen, L.O.; Husted, H.; Otte, K.S.

2008-01-01

with a detailed description of the infiltration technique. METHODS: In a randomized, double-blind, placebo-controlled trial in 12 patients undergoing bilateral knee arthroplasty, saline or high-volume (170 ml) ropivacaine (0.2%) with epinephrine was infiltrated around each knee, with repeated doses administered...

Effect of oral administration of freshly pressed juice of Echinacea purpurea on the number of various subpopulations of B- and T-lymphocytes in healthy volunteers: results of a double-blind, placebo-controlled cross-over study

DEFF Research Database (Denmark)

Schwarz, Evelyn; Parlesak, Alexandr; Henneicke-von-Zeppelin, H. H.

2005-01-01

BACKGROUND: In a recent double-blind placebo-controlled crossover-study the "immune stimulatory" effects (activation of macrophages leading to enhanced phagocytosis and production of several cytokines) of Echinacea purpurea preparations (EPP) which were observed in vitro experiments and following...

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

NARCIS (Netherlands)

Jairath, Vipul; Zou, Guangyong; Parker, Claire E.; Macdonald, John K.; Mosli, Mahmoud H.; Khanna, Reena; Shackelton, Lisa M.; Vandervoort, Margaret K.; AlAmeel, Turki; Al Beshir, Mohammad; AlMadi, Majid; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas P.; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel; Koutsoumpas, Andreas; Minas, Elizabeth; Samaan, Mark A.; Travis, Simon; D'Haens, Geert; Levesque, Barrett G.; Sandborn, William J.; Feagan, Brian G.

2016-01-01

Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

Science.gov (United States)

Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

2016-06-01

Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study; a multicenter randomized placebo controlled trial

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Onland Wes

2011-11-01

Full Text Available Abstract Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD. However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR: NTR2768

Varenicline for opioid withdrawal in patients with chronic pain: a randomized, single-blinded, placebo controlled pilot trial.

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Hooten, W Michael; Warner, David O

2015-03-01

The objectives of this randomized, single-blinded, placebo-controlled pilot trial were to investigate the effects of varenicline on opioid withdrawal among chronic pain patients undergoing opioid detoxification in an interdisciplinary pain program and the feasibility of varenicline use in this population. Twenty-one patients were recruited (varenicline=10, placebo=11), and 7 patients in the varenicline and 11 in the placebo group completed the study. Opioid withdrawal was quantified using the Clinical Opiate Withdrawal Scale, and varenicline-related adverse effects were assessed. Opioid withdrawal scores tended to decrease over the course of opioid tapering in those receiving varenicline and increase in those receiving placebo. Varenicline was well-tolerated in this population, with no adverse drug effects (including nausea) observed and no effect on improvements in pain severity and depression. This randomized pilot study provides preliminary data for future trials of varenicline in opioid-dependent adults with chronic pain undergoing medically directed opioid detoxification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of almond consumption on vascular function in patients with coronary artery disease: a randomized, controlled, cross-over trial

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Objective: Almonds reduce cardiovascular disease risk via cholesterol reduction, anti-inflammation, glucoregulation, and antioxidation. The objective of this randomized, controlled, cross-over trial was to determine whether the addition of 85 g almonds daily to a National Cholesterol Education Progr...

A Phase 3 Placebo-Controlled, Double Blind, Multi-Site Trial of the alpha-2-adrenergic Agonist, Lofexidine, for Opioid Withdrawal

Science.gov (United States)

Yu, Elmer; Miotto, Karen; Akerele, Evaristo; Montgomery, Ann; Elkashef, Ahmed; Walsh, Robert; Montoya, Ivan; Fischman, Marian W.; Collins, Joseph; McSherry, Frances; Boardman, Kathy; Davies, David K.; O’Brien, Charles P.; Ling, Walter; Kleber, Herbert; Herman, Barbara H.

2008-01-01

Context Lofexidine is an alpha-2-A noradrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. Objective To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally-defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. Design An inpatient, Phase 3, placebo-controlled, double blind, randomized multi-site trial with three phases: (1) Opioid Agonist Stabilization Phase (days 1–3), (2) Detoxification/Medication or Placebo Phase (days 4–8), and (3) Post Detoxification/Medication Phase (days 9–11). Subjects Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. Main Outcome Measure Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (2nd opioid detoxification treatment day). Results Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (Least squares means 19.5 ± 2.1 versus 30.9 ± 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. Trial Registration trial registry name A Phase 3 Placebo-Controlled, Double-Blind Multi-Site Trial of Lofexidine for Opiate Withdrawal, registration number NCT00032942, URL for the registry http://clinicaltrials.gov/ct/show/NCT00032942?order=4. PMID:18508207

Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

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Chang Anne B

2012-08-01

Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review

DEFF Research Database (Denmark)

Hougaard, Anders; Tfelt-Hansen, Peer

2016-01-01

of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying...... reports of RCTs. RESULTS: A placebo arm was used in requiring more than 75,000 patient days, no difference...... was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine...

Trial of early noninvasive ventilation for ALS: A pilot placebo-controlled study.

Science.gov (United States)

Jacobs, Teresa L; Brown, Devin L; Baek, Jonggyu; Migda, Erin M; Funckes, Timothy; Gruis, Kirsten L

2016-11-01

To evaluate the use and tolerability of noninvasive positive pressure ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS) early in their disease by comparing active NIV and sham NIV in patients not yet eligible for NIV use as recommended by practice guidelines. This was a single-center, prospective, double-blind, randomized, placebo (sham)-controlled pilot trial. Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC) NIV for clinical symptom management. In total, 54 participants were randomized. The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1-3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0-4.6) per day in the active NIV group, which did not differ by treatment group (p = 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p = 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups. The efficacy of early NIV in ALS should be tested in randomized, placebo-controlled trials. The trial is registered on clinicaltrials.gov (NCT00580593). This study provides Class II evidence that for patients with ALS, adherence with NIV and sham NIV are similar. © 2016 American Academy of Neurology.

Propranolol, clonidine, urapidil and trazodone infusion in essential tremor: a double-blind crossover trial.

Science.gov (United States)

Caccia, M R; Osio, M; Galimberti, V; Cataldi, G; Mangoni, A

1989-05-01

Accelerometric tremorgrams were recorded from 25 subjects affected by essential tremor and analysed by a Berg-Fourier frequency analyser before and during venous infusion of the following drugs: propranolol (beta-blocker), clonidine (alpha-presynaptic adrenergic agonist), urapidil (alpha-postsynaptic blocker), trazodone (adrenolytic agent) and placebo. The washout interval between infusions was 3 days. Recordings and data analyses were performed in a double-blind crossover trial. Tremor was classified as: at rest; postural (arms hyperextended); and intention (finger-nose test). Analysis of the results showed that propranolol and clonidine reduced significantly (P = 0.01 and P = 0.009, respectively) the power spectrum of postural tremor, but left at rest and intention tremors unchanged. No significant effects on the tremor power spectrum were observed after placebo, urapidil or trazodone administration. None of the drugs had any effect on tremor frequency.

A double-blind, randomized, placebo-controlled trial studying the effects of Saccharomyces boulardii on the gastrointestinal tolerability, safety, and pharmacokinetics of miglustat.

Science.gov (United States)

Remenova, Tatiana; Morand, Olivier; Amato, Dominick; Chadha-Boreham, Harbajan; Tsurutani, Scott; Marquardt, Thorsten

2015-06-19

Gastrointestinal (GI) disturbances such as diarrhea and flatulence are the most frequent adverse effects associated with miglustat therapy in type 1 Gaucher disease (GD1) and Niemann-Pick disease type C (NP-C), and the most common recorded reason for stopping treatment during clinical trials and in clinical practice settings. Miglustat-related GI disturbances are thought to arise from the inhibition of intestinal disaccharidases, mainly sucrase isomaltase. We report the effects of a co-administered dietary probiotic, S. boulardii, on the GI tolerability of miglustat in healthy adult subjects. In a double-blind, placebo-controlled, two-period, two-treatment cross-over trial, healthy adult male and female subjects were randomly allocated to treatment sequences, A-B and B-A (treatment A - miglustat 100 mg t.i.d. + placebo; treatment B - miglustat 100 mg t.i.d. + S. boulardii [500 mg, b.i.d.]). GI tolerability data were collected in patient diaries. The primary endpoint was the total number of 'diarrhea days' (≥3 loose stools within a 24-h period meeting Bristol Stool Scores [BSS] 6-7) based on WHO criteria. Secondary endpoints comprised numerous other diarrhea and GI tolerability indices. Twenty-one subjects received randomized therapy in each treatment sequence (total N = 42), and overall, 37 (88 %) subjects completed the study. The total number of diarrhea days was boulardii (0.8 [2.4] days) than with miglustat + placebo (1.3 [2.4] days), but the paired treatment difference was not statistically significant (-0.5 [2.4] days; p = 0.159). However, a significant treatment difference (-0.7 [1.9]; p boulardii (73 %). There were no between-treatment differences in miglustat pharmacokinetics. Although the primary endpoint was not met, the results of the post-hoc analysis suggest that co-administration of miglustat with S. boulardii might improve GI tolerability.

Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

Science.gov (United States)

Bennell, K; Hinman, R; Metcalf, B; Buchbinder, R; McConnell, J; McColl, G; Green, S; Crossley, K

2005-01-01

Objective: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. Methods: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Results: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: –2.2 cm (95% CI, –2.6 to –1.7) and –2.0 cm (–2.5 to –1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: –2.1 (–2.6 to –1.6) and –1.6 (–2.2 to –1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). Conclusions: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability. PMID:15897310

Characteristics of Placebo Responders in Pediatric Clinical Trials of Attention-Deficit/Hyperactivity Disorder

Science.gov (United States)

Newcorn, Jeffrey H.; Sutton, Virginia K.; Zhang, Shuyu; Wilens, Timothy; Kratochvil, Christopher; Emslie, Graham J.; D'Souza, Deborah N.; Schuh, Leslie M.; Allen, Albert J.

2009-01-01

Objective: Understanding placebo response is a prerequisite to improving clinical trial methodology. Data from placebo-controlled trials of atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were analyzed to identify demographic and clinical characteristics that might predict placebo…

Topical glyceryl trinitrate treatment of chronic patellar tendinopathy : a randomised, double-blind, placebo-controlled clinical trial

NARCIS (Netherlands)

Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam

Objectives To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Methods Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN

Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial

NARCIS (Netherlands)

Padberg, M.; de Bruijn, S. F. T. M.; de Haan, R. J.; Tavy, D. L. J.

2004-01-01

Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum

A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa

DEFF Research Database (Denmark)

Miller, I; Lynggaard, C D; Lophaven, S

2011-01-01

BACKGROUND: Hidradenitis suppurativa (HS) has an impact on patients' quality of life. Treatment of HS is generally unsatisfactory, thus new treatments are needed. OBJECTIVES: To test the efficacy of adalimumab in HS. METHODS: This was a prospective, randomized, double-blinded, placebo-controlled,......BACKGROUND: Hidradenitis suppurativa (HS) has an impact on patients' quality of life. Treatment of HS is generally unsatisfactory, thus new treatments are needed. OBJECTIVES: To test the efficacy of adalimumab in HS. METHODS: This was a prospective, randomized, double-blinded, placebo......-controlled, two-centre clinical trial conducted in Denmark. Inclusion criteria were age above 18 years and a clinical diagnosis of moderate to severe HS defined as Hurley stage II or III for at least 6 months. The patients were randomized 1:2 (placebo/active). Actively treated patients received adalimumab 80 mg...... subcutaneously (s.c.) at baseline followed by 40 mg s.c. every other week for 12 weeks. Placebo-treated patients received identical-looking injections with no active ingredient. The medicine was dispensed in sequentially numbered computer-randomized containers. Participants, care givers and those assessing...

Predictive factors for the placebo effect in clinical trials for dry eye: a pooled analysis of three clinical trials.

Science.gov (United States)

Imanaka, Takahiro; Sato, Izumi; Tanaka, Shiro; Kawakami, Koji

2017-11-01

Placebo effect is one of the methodological difficulties in dry eye clinical trials. If we could elucidate the tendencies of the placebo response and find predictors, we could reduce the placebo response in clinical trials for dry eye. In this study, we investigated the predictive factors for the placebo effect in dry eye clinical trials. A total of 205 patients with dry eye assigned to the placebo arms of three placebo-controlled randomised clinical trials were analysed by simple and multivariable regression analysis. The corneal fluorescein (FL) staining score and dry eye symptoms were studied at week 4. The variables of interest included gender, age, complications of Sjögren's syndrome, Schirmer's test I value, tear break-up time and conjunctival hyperaemia score. We also conducted a stratified analysis according to the patients' age. Among all the studied endpoints, the baseline scores were significantly related to the corresponding placebo response. In addition, for the FL score and the dryness score, age was a significant predictor of the placebo response (p=0.04 and p<0.0001, respectively). Stratified analysis by age showed that patients more than 40 years of age are more likely to have a stronger placebo response in the FL and dryness scores. The baseline scores and age were predictive factors of the placebo response in frequently used endpoints, such as FL score or dryness symptoms. These patient characteristics can be controlled by study design, and our findings enable the design of more efficient placebo-controlled studies with good statistical power. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial

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Tania Cursino de Menezes Couceiro

2015-06-01

Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.

Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study

Directory of Open Access Journals (Sweden)

Ravn P

2013-01-01

Full Text Available Pernille Ravn,1 Erik L Secher,2 Ulrik Skram,3 Trine Therkildsen,1 Lona L Christrup,1 Mads U Werner41Department of Drug Design and Pharmacology, University of Copenhagen, 2Department of Anesthesiology, Juliane Marie Center, Rigshospitalet, Copenhagen University Hospitals, 3Department of Intensive Care, Gentofte Hospital, Copenhagen University Hospitals, 4Multidisciplinary Pain Center, Neuroscience Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, DenmarkPurpose: Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than µ-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation.Subjects and methods: Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg, buprenorphine (0.3/0.6 mg, or placebo (normal saline were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm2, and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist.Results: For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia

Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study

International Nuclear Information System (INIS)

Incrocci, Luca; Koper, Peter C.M.; Hop, Wim C.J.; Slob, A. Koos

2001-01-01

Purpose: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. Results: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. Conclusion: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer

Maintenance nifedipine therapy for preterm symptomatic placenta previa: A randomized, multicenter, double-blind, placebo-controlled trial.

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Eric Verspyck

Full Text Available To assess the impact of maintenance nifedipine therapy on pregnancy duration in women with preterm placenta previa bleeding.PPADAL was a randomized, double-blind, placebo-controlled trial conducted between 05/2008 and 05/2012 in five French hospitals. The trial included 109 women, aged ≥ 18 years, with at least one episode of placenta previa bleeding, intact membranes and no other pregnancy complication, at gestational age 24 to 34 weeks and after 48 hours of complete acute tocolysis. Women were randomly allocated to receive either 20 mg of slow-release nifedipine three times daily (n = 54 or placebo (n = 55 until 36 + 6 weeks of gestation. The primary outcome for the trial was length of pregnancy measured in days after enrolment. Main secondary outcomes were rates of recurrent bleeding, cesarean delivery due to hemorrhage, blood transfusion, maternal side effects, gestational age at delivery and adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage > grade 2, perventricular leukomalacia > grade 1, or necrotizing enterocolitis. Analysis was by intention to treat.Mean (SD prolongation of pregnancy was not different between the nifedipine (n = 54 and the placebo (n = 55 group; 42.5 days ± 23.8 versus 44.2 days ± 24.5, p = 0.70. Cesarean due to hemorrhage performed before 37 weeks occurred more frequently in the nifedipine group in comparison with the placebo group (RR, 1.66; 95% confidence interval, 1.05-2.72. Adverse perinatal outcomes were comparable between groups; 3.8% for nifedipine versus 5.5% for placebo (relative risk, 0.52; 95% confidence interval 0.10-2.61. No maternal mortality or perinatal death occurred.Maintenance oral nifedipine neither prolongs duration of pregnancy nor improves maternal or perinatal outcomes.ClinicalTrials.gov NCT00620724.

Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial.

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Hohlfeld, Jens M; Vogel-Claussen, Jens; Biller, Heike; Berliner, Dominik; Berschneider, Korbinian; Tillmann, Hanns-Christian; Hiltl, Simone; Bauersachs, Johann; Welte, Tobias

2018-02-21

Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA-inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic. Eligible participants were patients aged at least 40 years with COPD, pulmonary hyperinflation (defined by a baseline residual volume >135% of predicted), a smoking history of at least ten pack-years, and airflow limitation (FEV 1 <80% predicted and post-bronchodilator FEV 1 : forced vital capacity <0·7). Patients with stable cardiovascular disease were eligible, but those with arrhythmias, heart failure, unstable ischaemic heart disease, or uncontrolled hypertension were not. We randomly assigned participants (1:1) to either receive a combined inhaled dual bronchodilator containing the LABA indacaterol (110 μg as maleate salt) plus the LAMA glycopyrronium (50 μg as bromide salt) once per day for 14 days, followed by a 14-day washout, then a matched placebo for 14 days, or to receive the same treatments in reverse order. The randomisation was done using lists and was concealed from patients and investigators. The primary endpoint was the effect of indacaterol-glycopyrronium versus placebo on left-ventricular end-diastolic volume measured by MRI done on day 1 (visit 4) and day 15 (visit 5) in treatment period 1 and on day 29 (visit 6) and day 43 (visit 7) in treatment period 2 in the per-protocol population. Left-ventricular end-diastolic volume was indexed to body surface area. Safety was assessed in all participants who received

Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial

NARCIS (Netherlands)

S. Koning (Sander); L.W.A. van Suijlekom-Smit (Lisette); J.L. Nouwen (Jan); C.M. Verduin (Cees); R.M.D. Bernsen (Roos); A.P. Oranje (Arnold); S. Thomas (Siep); J.C. van der Wouden (Hans)

2002-01-01

textabstractOBJECTIVE: To test the hypothesis that fusidic acid would not increase the treatment effect of disinfecting with povidone-iodine alone in children with impetigo. DESIGN: Randomised placebo controlled trial. SETTING: General practices in Greater Rotterdam.

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant in patients with traumatic brain injury

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Rätsep Indrek

2009-12-01

Full Text Available Abstract Background Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Methods Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE, mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS, the Disability Rating Scale (DRS and a modified version of the Oxford Handicap Scale (HIREOS. Results 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163 in the combined Anatibant treated group, compared to 19.3% (11/57 in the placebo group (relative risk = 1.37; 95% CI 0·76 to 2·46. All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36. The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. Conclusion This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in

Femicomfort in the Treatment of Premenstrual Syndromes: A Double-Blind, Randomized and Placebo Controlled Trial

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Shahin Akhondzadeh

2010-06-01

Full Text Available "nObjective:Premenstrual syndromes (PMS affecting 20-40% of women of reproductive age. The aim of this double blind and placebo controlled trial was to investigate whether femicofort a supplement contains Vitamin B6, Vitamin E and evening primrose oil could relieve symptoms of PMS. "nMethod: This was a randomized and double blind clinical trial. The trial was conducted between November 2009 and April March 2010. Women aged 20 to 45 years with regular menstrual cycles and experience of PMS symptoms (According to the current diagnostic criteria proposed by the American College of Obstetrics and Gynecology for at least 6 months were eligible for the study. Patients were randomized to receive femicomfort or placebo in a 1: ratio using a computer-generated code. The assignments were kept in sealed, opaque envelopes until the point of analysis of data. In this double-blind, patients were randomly assigned to receive capsule of femicomfort (Group A or capsule placebo for two menstrual cycles (cycles 3 and 4. The primary outcome measure was the Daily Symptom Report, a checklist of 17 premenstrual symptoms rated from 0 to 4 according to their severity throughout the menstrual cycle. Secondary outcome measure was Hamilton Depression Rating Scale (17-item. "nResults:Femicomfort at this dose was found to be effective in relieving symptoms of PMS. The difference between the femicomfort and placebo in the frequency of side effects was not significant. Conclusion: The results of this study indicate the efficacy of femicomfort in the treatment of PMS.

Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial

NARCIS (Netherlands)

van der Bom, Teun; Winter, Michiel M.; Bouma, Berto J.; Groenink, Maarten; Vliegen, Hubert W.; Pieper, Petronella G.; van Dijk, Arie P. J.; Sieswerda, Gertjan T.; Roos-Hesselink, Jolien W.; Zwinderman, Aeilko H.; Mulder, Barbara J. M.

2013-01-01

The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a

Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II

NARCIS (Netherlands)

Versyck, B.; Geffen, G.J. van; Houwe, P. Van

2017-01-01

STUDY OBJECTIVE: The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. DESIGN: A prospective randomized double blind placebo-controlled study. SETTING:

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

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Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

2015-02-01

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; Pefficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics

NARCIS (Netherlands)

Selle, V.; Schalkwijk, S.J.; Vazquez, G.H.; Baldessarini, R.J.

2014-01-01

BACKGROUND: Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. METHODS: We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants,

Effects of trans fatty acids on glucose homeostasis: a meta-analysis of randomized, placebo-controlled clinical trials123

OpenAIRE

Aronis, Konstantinos N; Khan, Sami M; Mantzoros, Christos S

2012-01-01

Background: Although evidence from cohort studies has suggested that trans fatty acid (TFA) consumption may be associated with insulin resistance and diabetes, randomized placebo-controlled trials (RCTs) have yielded conflicting results.

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

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Claustrat Bruno

2010-06-01

Full Text Available Abstract Background To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ in subjects with moderate to severe sleep disorders. Methods Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group or olive oil (placebo group for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii night melatonin and 6 sulfatoxymelatonin (aMT6S urine rates in a subsample of subjects. Results The average of Leeds score was similar in both groups (p = 0.95. A marked improvement in the quality of sleep was observed in both placebo (62% and active (65% group (p = 0.52. The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91. Conclusions The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle. Trial registration: clinical trials.gov:NCT00484497

A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

International Nuclear Information System (INIS)

Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

2014-01-01

Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial.

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Sahraian, Ali; Ghanizadeh, Ahmad; Kazemeini, Fereshteh

2015-03-14

There are some animal studies suggesting the possible role of vitamin C for treating depression. However, the efficacy of vitamin C for treating adult patients with major depressive disorder (MDD) has never been examined. This 8-week randomized double-blind placebo-controlled clinical trial included adult patients with major depressive disorder according to DSM-IV diagnostic criteria. Twenty-one patients in the treatment group received citalopram plus vitamin C and the 22 patients in the control group received citalopram plus placebo. The Hamilton Depression Rating Scale was used to measure depressive symptoms at baseline, week 2, week 4, and week 8. We also checked for the presence of adverse effects. While depression symptoms decreased in both groups during this trial, there was no statistically significant difference between the 2 groups (P = .5). The rate of remission, partial response, and complete response was not different between the two groups. The rate of adverse effects were not different between the two groups. Adding vitamin C to citalopram did not increase the efficacy of citalopram in MDD patients. Vitamin C plus citalopram is as effective as placebo plus citalopram for treating adult patients with suicidal behavior. No serious adverse effect for this combination was identified during this trial. This trial was registered at http://www.irct.ir . The registration number of this trial was: IRCT201312263930N31 . Date registered: 5 July 2014.

Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.

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Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

2015-02-01

Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

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Necek Magdalena

2008-05-01

Full Text Available Abstract Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713

Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST).

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Pressman, Alice; Avins, Andrew L; Neuhaus, John; Ackerson, Lynn; Rudd, Peter

2012-05-01

Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by reanalyzing data from the placebo arm of the Beta Blocker Evaluation of Survival Trial (BEST), a randomized, double-blind, placebo-controlled trial of bucindolol and mortality. Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the BEST trial. Secondary aims included assessment of the association between placebo adherence and cause-specific mortality. Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication over the entire course of each individual's participation in the study, while those with "lower placebo adherence" took <75%. Primary outcome was in-study all-cause mortality. To account for confounding, we adjusted for all available modifiable, non-modifiable and psychosocial variables. Adherent participants had a significantly lower total mortality compared to less-adherent participants (HR=0.61, 95% Confidence Interval: 0.46-0.82). Adjusting for available confounders did not change the magnitude or significance of the estimates. When considering cause-specific mortality, CVD and pump failure showed similar associations. Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery. Prospective examination of this association is necessary to better understand the underlying mechanism of this observation. Copyright © 2012 Elsevier Inc. All rights reserved.

Randomized, double-blinded, placebo-controlled trial comparing two multimodal opioid-minimizing pain management regimens following transsphenoidal surgery.

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Shepherd, Deborah M; Jahnke, Heidi; White, William L; Little, Andrew S

2018-02-01

OBJECTIVE Pain control is an important clinical consideration and quality-of-care metric. No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions. The study goals were to 1) report postoperative pain scores following transsphenoidal surgery, 2) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control, and 3) determine if intravenous (IV) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo. METHODS This study was a single-center, randomized, double-blinded, placebo-controlled intervention trial involving adult patients with planned transsphenoidal surgery for pituitary tumors randomized into 2 groups. Group 1 patients were treated with scheduled IV ibuprofen, scheduled oral acetaminophen, and rescue opioids. Group 2 patients were treated with IV placebo, scheduled oral acetaminophen, and rescue opioids. The primary end point was patient pain scores (visual analog scale [VAS], rated 0-10) for 48 hours after surgery. The secondary end point was opioid use as estimated by oral morphine equivalents (OMEs). RESULTS Of 136 patients screened, 62 were enrolled (28 in Group 1, 34 in Group 2). The study was terminated early because the primary and secondary end points were reached. Baseline characteristics between groups were well matched except for age (Group 1, 59.3 ± 14.4 years; Group 2, 49.8 ± 16.2 years; p = 0.02). Mean VAS pain scores were significantly different, with a 43% reduction in Group 1 (1.7 ± 2.2) compared with Group 2 (3.0 ± 2.8; p transsphenoidal surgery. IV ibuprofen resulted in significantly improved pain scores and significantly decreased opioid use compared with placebo. Postoperative multimodal pain management, including a nonsteroidal antiinflammatory medication, should be considered after surgery to improve patient comfort and to limit opioid use. Clinical trial registration no.: NCT02351700 (clinicaltrials

Effects of polydextrose with breakfast or with a midmorning preload on food intake and other appetite-related parameters in healthy normal-weight and overweight females: An acute, randomized, double-blind, placebo-controlled, and crossover study.

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Ibarra, Alvin; Olli, Kaisa; Pasman, Wilrike; Hendriks, Henk; Alhoniemi, Esa; Raza, Ghulam Shere; Herzig, Karl-Heinz; Tiihonen, Kirsti

2017-03-01

Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs when PDX is given at breakfast time. Furthermore, for ecological validity, it is desirable to study a female population, including those at risk for obesity. We studied the effects of PDX, served as part of a breakfast or midmorning preload, on subsequent EI and other appetite-related parameters in healthy normal-weight and overweight females. Per earlier studies, the primary outcome was defined as the difference in subsequent EI when PDX was consumed at midmorning versus placebo. Thirty-two volunteers were enrolled in this acute, double-blind, placebo-controlled, randomized, and crossover trial to examine the effects of 12.5 g of PDX, administered as part of a breakfast or midmorning preload, on subsequent EI, subjective feelings of appetite, well-being, and mood. Gastric emptying rates and the blood concentrations of glucose, insulin, cholecystokinin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine-tyrosine were measured in the group that received PDX as part of their breakfast. There were no differences in EI between volunteers who were fed PDX and placebo. PDX intake with breakfast tended to elevate blood glucose (P = 0.06) during the postabsorptive phase, significantly lowered insulin by 15.7% (P = 0.04), and increased GLP-1 by 39.9% (P = 0.02); no other effects on blood parameters or gastric emptying rates were observed. PDX intake at midmorning reduced hunger by 31.4% during the satiation period (P = 0.02); all other subjective feelings of appetite were unaffected. Volunteers had a uniform mood profile during the study. PDX was well tolerated, causing one mild adverse event throughout the trial. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.

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Rezaei, Farzin; Ghaderi, Ebrahim; Mardani, Roya; Hamidi, Seiran; Hassanzadeh, Kambiz

2016-06-01

To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index (ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group (P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity (P methamphetamine dependence. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial.

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Jill M Hamilton-Reeves

Full Text Available We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA, hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer.We conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n=42 or placebo (n=44 for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant.These data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA.ClinicalTrials.gov NCT00255125.

Randomized, Double-Blind, Crossover Trial of Amitriptyline for Analgesia in Painful HIV-Associated Sensory Neuropathy.

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Natalya Dinat

Full Text Available We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i antiretroviral drug naive individuals, and ii antiretroviral drug users. 124 HIV-infected participants (antiretroviral drug naive = 62, antiretroviral drug users = 62 who met the study criteria for painful HIV-associated sensory neuropathy were randomized to once-daily oral amitriptyline (titrated to a median: interquartile range of 50: 25-50 mg or placebo for six weeks, followed by a three-week washout period and subsequent treatment crossover. The primary outcome measure was change from baseline in worst pain intensity of the feet (measured by participant self-report using an 11-point numerical pain rating scale after six weeks of treatment. 122 of 124 participants completed all study visits and were included in the analysis of the primary outcome. In the antiretroviral drug-naive group (n = 61 there was no significant difference in the mean change in pain score from baseline after six weeks of treatment with placebo or amitriptyline [amitriptyline: 2.8 (SD 3.3 vs. placebo: 2.8 (3.4]. Similarly, there was no significant difference in the change in pain score after six weeks of treatment with placebo or amitriptyline in the antiretroviral drug-user group (n = 61 [amitriptyline: 2.7 (3.3 vs. placebo: 2.1 (2.8]. Controlling for period effects and treatment order effects did not alter the outcome of the analyses. Nor did analyzing the intention-to-treat cohort (missing data interpolated using baseline observation carried forward alter the outcome of the analyses. In summary, amitriptyline, at the doses used here, was no more effective than an inactive placebo at reducing pain intensity in individuals with painful HIV-associated sensory neuropathy of moderate to severe intensity, irrespective of

Sucralfate mouthwash for prevention and treatment of 5-fluorouracil-induced mucositis: a randomized, placebo-controlled trial.

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Nottage, Michelle; McLachlan, Sue-Anne; Brittain, Mary-Anne; Oza, Amit; Hedley, David; Feld, Ronald; Siu, Lillian L; Pond, Gregory; Moore, Malcolm J

2003-01-01

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of a sucralfate mouthwash in preventing and alleviating oral mucositis induced by 5-fluorouracil (5FU). A total of 81 patients with colorectal cancer were enrolled. Patients were studied during their first cycle of chemotherapy with 5FU and leucovorin (LV) daily for 5 days every 4 weeks (Mayo Clinic schedule). Patients were randomly allocated to receive either a sucralfate suspension or a placebo suspension that was identical in appearance. Patients were instructed to use the suspension as a mouthwash four times daily from the beginning of the chemotherapy cycle. All patients received oral cryotherapy. Patients graded the severity of their own symptoms on a daily basis, and this was the primary outcome measure. There was no difference in the frequency or severity of oral mucositis between the sucralfate- and the placebo-treated group. Some mucositis was reported by 79% of the patient group. Assessment of mucositis by trial staff underestimated the incidence of this problem. Results of this trial do not support the hypothesis that a sucralfate mouthwash can prevent or alleviate oral mucositis induced by 5FU. Patient reporting of mucositis is a more sensitive instrument for assessment of mucositis than review by medical staff.

Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial.

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Chollet, François; Tardy, Jean; Albucher, Jean-François; Thalamas, Claire; Berard, Emilie; Lamy, Catherine; Bejot, Yannick; Deltour, Sandrine; Jaillard, Assia; Niclot, Philippe; Guillon, Benoit; Moulin, Thierry; Marque, Philippe; Pariente, Jérémie; Arnaud, Catherine; Loubinoux, Isabelle

2011-02-01

Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial

Placebo response and remission rates in randomised trials of induction andmaintenance therapy for ulcerative colitis

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Jairath, Vipul; Zou, G. Y.; Parker, Claire E.; Macdonald, John K.; AlAmeel, Turki; Al Beshir, Mohammad; Almadi, Majid A.; Al-Taweel, Talal; Atkinson, Nathan S. S.; Biswas, Sujata; Chapman, Thomas; Dulai, Parambir S.; Glaire, Mark A.; Hoekman, Daniel R.; Koutsoumpas, Andreas; Minas, Elizabeth; Mosli, Mahmoud H.; Samaan, Mark; Khanna, Reena; Travis, Simon; D'Haens, Geert; Sandborn, William J.; Feagan, Brian G.

2017-01-01

Background It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors

Sono-electro-magnetic therapy for treating chronic pelvic pain syndrome in men: a randomized, placebo-controlled, double-blind trial.

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Thomas M Kessler

Full Text Available OBJECTIVE: To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. PATIENTS AND METHODS: In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30 or placebo therapy (n = 30 for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI from baseline to 12 weeks. RESULTS: The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was -3.1 points (95% CI -6.8 to 0.6, p = 0.11. In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks -1.6, 95% CI -2.8 to -0.4, p = 0.015. In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score -8.3, 95% CI -14.5 to 2.6 than in patients with a longer symptom duration (-0.8, 95% CI -4.6 to 3.1; p for interaction = 0.023. CONCLUSIONS: Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00688506.

A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.

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Schoenberg, Mike R; Rum, Ruba S; Osborn, Katie E; Werz, Mary Ann

2017-09-01

The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance. Wiley Periodicals, Inc. © 2017 International

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury.

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Shakur, Haleema; Andrews, Peter; Asser, Toomas; Balica, Laura; Boeriu, Cristian; Quintero, Juan Diego Ciro; Dewan, Yashbir; Druwé, Patrick; Fletcher, Olivia; Frost, Chris; Hartzenberg, Bennie; Mantilla, Jorge Mejia; Murillo-Cabezas, Francisco; Pachl, Jan; Ravi, Ramalingam R; Rätsep, Indrek; Sampaio, Cristina; Singh, Manmohan; Svoboda, Petr; Roberts, Ian

2009-12-03

Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial

A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women.

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Jordan E Bisanz

Full Text Available A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains.ClinicalTrials.gov NCT02139839.

Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomnia.

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Kohsaka, Masako; Kanemura, Takashi; Taniguchi, Mitsutaka; Kuwahara, Hiroo; Mikami, Akira; Kamikawa, Kunihisa; Uno, Hideki; Ogawa, Atsushi; Murasaki, Mitsukuni; Sugita, Yoshiro

2011-10-01

The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

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Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C

2016-02-01

Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. Published by Elsevier Ireland Ltd.

Double blind, placebo-controlled trial of Tranexamic acid on recent internal hemorrhoid bleeding

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Abdul A. Rani

2002-12-01

Full Text Available Double blind randomized placebo controlled trial was conducted to evaluate the efficacy of Tranexamic acid in 54 patients with recent hemorrhoid bleeding. Age, gender, body weight, height, grade of hemorrhoid, time of onset of recent bleeding were comparable between two groups. Analysis of haemostatic effect or stop bleeding as an immediate outcome of this study revealed that in the grade 2 patients, 23/23 (100% of tranexamic group and 18/23(78.26% of placebo group the bleeding stop. After 3 days of observation, there was statistically significant different for the rate of stop bleeding as well as at the end of observation. Bleeding stop earlier in the Tranexamic group with median 4 days (3-5 days, compare to placebo, median 11(9.55-12.45. Analysis of recurrent bleeding as an outcome of this study revealed that in the placebo group 9/18(50% of grade 2 patients and all grade 3 (100%patients suffered from recurrent bleeding. Since the days 4, both group have significant different time for recurrent bleeding and at the end of observation, cumulative probability of free of bleeding between two groups significantly different. Median still stop bleeding in the placebo group was 36 days, and the tranexamic group never reaches the median until the end of observation. Conclusion: tranexamic acid was an effective drug to stop recent hemorrhoid bleeding and prevent further recurrent bleeding, significantly better than placebo. (Med J Indones 2002;11: 215-21Keywords: Tranexamic acid, hemorrhoid bleeding, haemostatic effect, recurrent bleeding.

Placebo controlled, crossover validation study of oral ibuprofen and topical hydrocortisone-21-acetate for a model of ultraviolet B radiation (UVR-induced pain and inflammation

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Rother M

2011-10-01

Full Text Available Matthias Rother, Ilka RotherDepartment of Clinical Operations, X-pert Med GmbH, Graefelfing, GermanyBackground: Pain related to ultraviolet B radiation (UVR induced sunburn is an established, simple, acute pain model. One of the major criticisms is related to the potential dermal adverse events caused by the UVR exposure. This study tried to validate the model for oral and topical drugs and to define the minimum required UVR exposure.Methods: This subject- and observer-blinded, placebo-controlled, crossover study evaluated 600 mg oral ibuprofen (IB and topical hydrocortisone-21-acetate (HC twice daily (bid in 24 healthy volunteers. Treatment started immediately after irradiation and again at 12 hours, 24 hours, and 36 hours post-UVR. Assessment of hyperalgesia to heat and signs of inflammation (erythema, skin temperature for all areas was performed after UVR and again at 6, 12, 24, 36, and 48 hours. Subjects returned within 4–11 days to the study site for the second period of the study. As in the first period, subjects received HC at one side and topical placebo on the other side, but oral treatment was crossed-over.Results: The primary analysis failed to show the expected superiority of the IB-group vs the placebo group in period 1 of the study. Evaluating period 2 alone clearly showed the expected treatment effects of IB for erythema and heat pain threshold. The results were less pronounced for skin temperature. In contrast to IB vs oral placebo, there were no differences in treatment response between HC and topical placebo. UVR at all dosages induced profound erythema and reduction of heat pain threshold without causing blisters or other unexpected discomfort to the subjects. The changes were almost linear between 1 and 2 minimal erythema doses (MED, whereas the change from 2 to 3 MED was less pronounced.Conclusion: Use of 2 MED in upcoming studies seems to be reasonable to limit subjects' UVB exposure. The following procedural changes are

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

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Wali, Ramesh K; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J; Rodriguez, L M; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K

2018-01-01

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. ClinicalTrials.gov NCT00828984.

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.

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Kennedy, Stephen B; Bolay, Fatorma; Kieh, Mark; Grandits, Greg; Badio, Moses; Ballou, Ripley; Eckes, Risa; Feinberg, Mark; Follmann, Dean; Grund, Birgit; Gupta, Swati; Hensley, Lisa; Higgs, Elizabeth; Janosko, Krisztina; Johnson, Melvin; Kateh, Francis; Logue, James; Marchand, Jonathan; Monath, Thomas; Nason, Martha; Nyenswah, Tolbert; Roman, François; Stavale, Eric; Wolfson, Julian; Neaton, James D; Lane, H Clifford

2017-10-12

The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (PLiberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).

A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal.

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Ajit Rayamajhi

Full Text Available Japanese encephalitis (JE virus (JEV is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial.We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group died during treatment and two (placebo subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2, which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.ClinicalTrials.gov NCT01856205.

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea.

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Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

2011-01-01

OBJECTIVE: To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). DESIGN: An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline 'trigger meals' and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. SETTING: Outpatient internal medicine practice clinic. PATIENTS: 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised 'food triggers', no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11-30 years and 16% for more than 40 years. INTERVENTIONS: After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. MAIN OUTCOME MEASURES: The primary analysis was number of patients who chose PEZ over placebo for the extended use. RESULTS: Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. CONCLUSIONS: PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation.

Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial.

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Samir K Gupta

Full Text Available Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed.The difference in mean absolute change (SD in FMD after 8 weeks between the placebo [-1.06 (1.45%] and PTX [-1.93 (3.03%] groups was not significant (P = 0.44. No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI [-83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated.PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.ClinicalTrials.gov NCT00796822.

No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

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Linares, Ila M P; Guimaraes, Francisco S; Eckeli, Alan; Crippa, Ana C S; Zuardi, Antonio W; Souza, Jose D S; Hallak, Jaime E; Crippa, José A S

2018-01-01

Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle. The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design. Twenty-seven healthy volunteers that fulfilled the eligibility criteria were selected and allocated to receive either CBD (300 mg) or placebo in the first night in a double-blind randomized design (one volunteer withdrew from the study). In the second night, the same procedure was performed using the substance that had not been administered in the previous occasion. CBD or placebo were administered 30 min before the start of polysomnography recordings that lasted 8 h. Cognitive and subjective measures were performed immediately after polysomnography to assess possible residual effects of CBD. The drug did not induce any significant effect ( p > 0.05). Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as in clinical trials with larger samples and chronic use of different doses of CBD. Such studies are desirable and opportune.

No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

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Ila M. P. Linares

2018-04-01

Full Text Available Cannabidiol (CBD is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle. The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design. Twenty-seven healthy volunteers that fulfilled the eligibility criteria were selected and allocated to receive either CBD (300 mg or placebo in the first night in a double-blind randomized design (one volunteer withdrew from the study. In the second night, the same procedure was performed using the substance that had not been administered in the previous occasion. CBD or placebo were administered 30 min before the start of polysomnography recordings that lasted 8 h. Cognitive and subjective measures were performed immediately after polysomnography to assess possible residual effects of CBD. The drug did not induce any significant effect (p > 0.05. Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as in clinical trials with larger samples and chronic use of different doses of CBD. Such studies are desirable and opportune.

Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.

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Sunay, Didem; Sunay, Melih; Aydoğmuş, Yasin; Bağbancı, Sahin; Arslan, Hüseyin; Karabulut, Ayhan; Emir, Levent

2011-05-01

Acupuncture therapy has been used by many researchers in both male and female sexual dysfunction studies. To determine whether acupuncture is effective as a premature ejaculation (PE) treatment compared with paroxetine and placebo. The study was conducted with methodologic rigor based on Consolidated Standards of Reporting Trials (CONSORT) criteria. Ninety patients referred to the urology clinic at a tertiary training and research hospital with PE were included in this randomized controlled trial and randomly assigned into paroxetine, acupuncture, and placebo groups. Heterosexual, sexually active men aged between 28 and 50 yr were included. Men with other sexual disorders, including erectile dysfunction; with chronic psychiatric or systemic diseases; with alcohol or substance abuse; or who used any medications were excluded. The medicated group received paroxetine 20 mg/d; the acupuncture or sham-acupuncture (placebo) groups were treated twice a week for 4 wk. Intravaginal ejaculation latency times (IELTs) and the Premature Ejaculation Diagnostic Tool (PEDT) were used to assess PE. IELTs were calculated by using a partner-held stopwatch. Data were analyzed statistically. Median PEDT scores of paroxetine, acupuncture, and placebo groups were 17.0, 16.0, and 15.5 before treatment, and 10.5, 11.0, and 16.0 after treatment, respectively (p=0.001, p=0.001, and p=0.314, respectively). Subscores after treatment were significantly lower than subscores before treatment in the paroxetine and acupuncture groups but remained the same in the placebo group. Significant differences were found between mean-rank IELTs of the paroxetine and placebo groups (p=0.001) and the acupuncture and placebo groups (p=0.001) after treatment. Increases of IELTs with paroxetine, acupuncture, and placebo acupuncture were 82.7, 65.7, and 33.1 s, respectively. Extent of ejaculation delay induced by paroxetine was significantly higher than that of acupuncture (p=0.001). The most important limitation

Homeopathic pathogenetic trials produce specific symptoms different from placebo.

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Möllinger, Heribert; Schneider, Rainer; Walach, Harald

2009-04-01

Homeopathy uses information gathered from healthy volunteers taking homeopathic substances (pathogenetic trials) for clinical treatment. It is controversial whether such studies produce symptoms different from those produced by placebo. To test whether homeopathic preparations produce different symptoms than placebo in healthy volunteers. Three armed, double-blind, placebo controlled randomised experimental pathogenetic study in 25 healthy volunteers who took either one of two homeopathic remedies, Natrum muriaticum and Arsenicum album in 30CH or identical placebo. Main outcome parameter was the number of remedy-specific symptoms per group. On average, 6 symptoms typical for Arsenicum album were experienced by participants taking arsenicum album, 5 symptoms typical for Natrum muriaticum by those taking natrum muriaticum, and 11 non-specific symptoms by those in the placebo group. Differences were significant overall (Kruskall Wallis test, p = 0.0002,) and significantly different from placebo (Mann-Whitney test, p = 0.001). Homeopathic remedies produce different symptoms than placebo. Copyright (c) 2009 S. Karger AG, Basel.

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration

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Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-01-01

groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications...... with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). Results The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0–2), 0.5% (0–1%). We identified...

Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial.

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Husain, Muhammad I; Chaudhry, Imran B; Husain, Nusrat; Khoso, Ameer B; Rahman, Raza R; Hamirani, Munir M; Hodsoll, John; Qurashi, Inti; Deakin, John Fw; Young, Allan H

2017-09-01

Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms. In this study, we aimed to investigate whether minocycline added to treatment as usual (TAU) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms. Multi-site, 12-week, double-blind, placebo-controlled, pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder, whose current episode has failed to respond to at least two antidepressants. The primary outcome measure was mean change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 12. Secondary measures were the Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder scale (GAD-7) and EuroQoL (EQ-5D) quality-of-life questionnaire. Side-effect checklists were also used. Minocycline was started at 100 mg once daily (OD) and increased to 200 mg after 2 weeks. A total of 41 participants were randomised, with 21 in the minocycline group and 20 in the placebo group. A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group (standardised effect size (ES) -1.21, p minocycline group also showed a large improvement compared with placebo (odds ratio (OR): 17.6, p minocycline leads to improvement in symptoms of treatment-resistant depression. However, our findings require replication in a larger sample. ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors.

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Leucht, Stefan; Leucht, Claudia; Huhn, Maximilian; Chaimani, Anna; Mavridis, Dimitris; Helfer, Bartosz; Samara, Myrto; Rabaioli, Matteo; Bächer, Susanne; Cipriani, Andrea; Geddes, John R; Salanti, Georgia; Davis, John M

2017-10-01

Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences. The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression. The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time. Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.

A placebo-controlled trial of itopride in functional dyspepsia.

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Holtmann, Gerald; Talley, Nicholas J; Liebregts, Tobias; Adam, Birgit; Parow, Christopher

2006-02-23

The treatment of patients with functional dyspepsia remains unsatisfactory. We assessed the efficacy of itopride, a dopamine D2 antagonist with anti-acetylcholinesterase [corrected] effects, in patients with functional dyspepsia. Patients with functional dyspepsia were randomly assigned to receive either itopride (50, 100, or 200 mg three times daily) or placebo. After eight weeks of treatment, three primary efficacy end points were analyzed: the change from baseline in the severity of symptoms of functional dyspepsia (as assessed by the Leeds Dyspepsia Questionnaire), patients' global assessment of efficacy (the proportion of patients without symptoms or with marked improvement), and the severity of pain or fullness as rated on a five-grade scale. We randomly assigned 554 patients; 523 had outcome data and could be included in the analyses. After eight weeks, 41 percent of the patients receiving placebo were symptom-free or had marked improvement, as compared with 57 percent, 59 percent, and 64 percent receiving itopride at a dose of 50, 100, or 200 mg three times daily, respectively (Pitopride). Although the symptom score improved significantly in all four groups, an overall analysis revealed that itopride was significantly superior to placebo, with the greatest symptom-score improvement in the 100- and 200-mg groups (-6.24 and -6.27, vs. -4.50 in the placebo group; P=0.05). Analysis of the combined end point of pain and fullness showed that itopride yielded a greater rate of response than placebo (73 percent vs. 63 percent, P=0.04). Itopride significantly improves symptoms in patients with functional dyspepsia. (ClinicalTrials.gov number, NCT00272103.). Copyright 2006 Massachusetts Medical Society.

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

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Beckman, Joshua A; Goldfine, Allison B; Leopold, Jane A; Creager, Mark A

2016-12-01

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus. Copyright © 2016 the American Physiological Society.

Effects of a mouthwash with chlorine dioxide on oral malodor and salivary bacteria: a randomized placebo-controlled 7-day trial

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Ohnuki Mari

2010-02-01

Full Text Available Abstract Background Previous research has shown the oxidizing properties and microbiological efficacies of chlorine dioxide (ClO2. Its clinical efficacies on oral malodor have been evaluated and reported only in short duration trials, moreover, no clinical studies have investigated its microbiological efficacies on periodontal and malodorous bacteria. Thus, the aim of this study was to assess the inhibitory effects of a mouthwash containing ClO2 used for 7 days on morning oral malodor and on salivary periodontal and malodorous bacteria. Methods/Design A randomized, double blind, crossover, placebo-controlled trial was conducted among 15 healthy male volunteers, who were divided into 2 groups. Subjects were instructed to rinse with the experimental mouthwash containing ClO2 or the placebo mouthwash, without ClO2, twice per day for 7 days. After a one week washout period, each group then used the opposite mouthwash for 7 days. At baseline and after 7 days, oral malodor was evaluated with Organoleptic measurement (OM, and analyzed the concentrations of hydrogen sulfide (H2S, methyl mercaptan (CH3SH and dimethyl sulfide ((CH32S, the main VSCs of human oral malodor, were assessed by gas chromatography (GC. Clinical outcome variables included plaque and gingival indices, and tongue coating index. The samples of saliva were microbiologically investigated. Quantitative and qualitative analyses were performed using the polymerase chain reaction-Invader method. Results and Discussion The baseline oral condition in healthy subjects in the 2 groups did not differ significantly. After rinsing with the mouthwash containing ClO2 for 7 days, morning bad breath decreased as measured by the OM and reduced the concentrations of H2S, CH3SH and (CH32S measured by GC, were found. Moreover ClO2 mouthwash used over a 7-day period appeared effective in reducing plaque, tongue coating accumulation and the counts of Fusobacterium nucleatum in saliva. Future research is

Demographic variables, design characteristics, and effect sizes of randomized, placebo-controlled, monotherapy trials of major depressive disorder and bipolar depression.

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Papakostas, George I; Martinson, Max A; Fava, Maurizio; Iovieno, Nadia

2016-05-01

The aim of this work is to compare the efficacy of pharmacologic agents for the treatment of major depressive disorder (MDD) and bipolar depression. MEDLINE/PubMed databases were searched for studies published in English between January 1980 and September 2014 by cross-referencing the search term placebo with each of the antidepressant agents identified and with bipolar. The search was supplemented by manual bibliography review. We selected double-blind, randomized, placebo-controlled trials of antidepressant monotherapies for the treatment of MDD and of oral drug monotherapies for the treatment of bipolar depression. 196 trials in MDD and 19 trials in bipolar depression were found eligible for inclusion in our analysis. Data were extracted by one of the authors and checked for accuracy by a second one. Data extracted included year of publication, number of patients randomized, probability of receiving placebo, duration of the trial, baseline symptom severity, dosing schedule, study completion rates, and clinical response rates. Response rates for drug versus placebo in trials of MDD and bipolar depression were 52.7% versus 37.5% and 54.7% versus 40.5%, respectively. The random-effects meta-analysis indicated that drug therapy was more effective than placebo in both MDD (risk ratio for response = 1.373; P depression (risk ratio = 1.257; P depression trials in favor of MDD (P = .008). Although a statistically significantly greater treatment effect size was noted in MDD relative to bipolar depression studies, the absolute magnitude of the difference was numerically small. Therefore, the present study suggests no clinically significant differences in the overall short-term efficacy of pharmacologic monotherapies for MDD and bipolar depression. © Copyright 2016 Physicians Postgraduate Press, Inc.

A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults

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Ha Ki-Chan

2012-02-01

Full Text Available Abstracts Background Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults. Methods/Design We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale. Discussion This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence. Trial Registration NCT01478009.

A double-blind placebo-controlled trial of maca root as treatment for antidepressant-induced sexual dysfunction in women.

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Dording, Christina M; Schettler, Pamela J; Dalton, Elizabeth D; Parkin, Susannah R; Walker, Rosemary S W; Fehling, Kara B; Fava, Maurizio; Mischoulon, David

2015-01-01

Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126.

A Double-Blind Placebo-Controlled Trial of Maca Root as Treatment for Antidepressant-Induced Sexual Dysfunction in Women

Directory of Open Access Journals (Sweden)

Christina M. Dording

2015-01-01

Full Text Available Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day in 45 female outpatients (mean age of 41.5 ± 12.5 years with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ. Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo, attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo. Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126.

Ethical Overview of Placebo Control in Psychiatric Research - Concepts and Challenges.

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Ćurković, Marko; Živković, Maja; Radić, Krešimir; Vilibić, Maja; Ćelić, Ivan; Bagarić, Dario

2015-06-01

Permissibility of placebo controls in psychiatric research is raising everlasting controversies. The main ethical issue remains: whether, when, under what conditions, and to what extent is it justifiable to disregard subject's present (best) interest for the presumably "greater" ones. In relation to this main ethical concern, two distinct arguments arose: proponents of placebo controls trials (placebo ortxodoxy) and proponents of active controls trials (active-control orthodoxy). More recently, in new ethical guidelines, Declaration of Helsinki and International Ethical Guidelines for Biomedical Research Involving Human Subjects, a "middle way" approach was formulated, acceptable to both sides of the argument, saying placebo controls can be justified under certain conditions: when and only when, they firstly present undisputed methodological reasoning, and secondly, fulfill certain ethical considerations - mainly regarding the permissibility of accompanied risks. These ethical evaluations are inevitably contextual and evoke the need for the principle of proportionality. In scope of recent findings of substantial and progressively increasing placebo response in psychiatric research, contextual factors are identified and both theoretical and practical challenges are discussed.

The administration to Indonesians of monosodium L-glutamate in Indonesian foods: an assessment of adverse reactions in a randomized double-blind, crossover, placebo-controlled study.

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Prawirohardjono, W; Dwiprahasto, I; Astuti, I; Hadiwandowo, S; Kristin, E; Muhammad, M; Kelly, M F

2000-04-01

Monosodium L-glutamate (MSG) has been suggested to cause postprandial symptoms after the ingestion of Chinese or oriental meals. Therefore, we examined whether such symptoms could be elicited in Indonesians ingesting levels of MSG typically found in Indonesian cuisine. Healthy volunteers (n = 52) were treated with capsules of placebo or MSG (1.5 and 3.0 g/person) as part of a standardized Indonesian breakfast. The study used a rigorous, randomized, double-blind, crossover design. The occurrence of symptoms after MSG ingestion did not differ from that after consumption of the placebo.

A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease

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Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; van Dyck, C.H.; Aisen, P.S.

2011-01-01

Background: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. Objective: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale–cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. Results: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. Conclusion: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. Classification of evidence: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog. PMID:21795660

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

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Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

2002-04-01

To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

Anti-hemorrhagic effect of prophylactic tranexamic acid in benign hysterectomy-a double-blinded randomized placebo-controlled trial

DEFF Research Database (Denmark)

Topsoee, Märta Fink; Bergholt, Thomas; Ravn, Pernille

2016-01-01

and in 2004, 8% of all women in Denmark undergoing benign hysterectomy experienced a bleeding complication. Tranexamic acid is an antifibrinolytic agent that has shown to effectively reduce bleeding complications within other surgical and medical areas. However, knowledge about the drug's effect in relation...... to benign hysterectomy is still missing. OBJECTIVE: To investigate the antihemorrhagic effect of prophylactic tranexamic acid in elective benign hysterectomy. STUDY DESIGN: A double-blinded randomized placebo-controlled trial was conducted at 4 gynecological departments in Denmark from April 2013 to October...... 2014. A total of 332 women undergoing benign abdominal, laparoscopic, or vaginal hysterectomy were included in the trial, randomized to either 1 g of intravenous tranexamic acid or placebo at start of surgery. Chi-square test and Student t test statistical analyses were applied. RESULTS: The primary...

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial.

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Cornu, Catherine; Remontet, Laurent; Noel-Baron, Florence; Nicolas, Alain; Feugier-Favier, Nathalie; Roy, Pascal; Claustrat, Bruno; Saadatian-Elahi, Mitra; Kassaï, Behrouz

2010-06-22

To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ) in subjects with moderate to severe sleep disorders. Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group) or olive oil (placebo group) for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i) perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii) sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii) night melatonin and 6 sulfatoxymelatonin (aMT6S) urine rates in a subsample of subjects. The average of Leeds score was similar in both groups (p = 0.95). A marked improvement in the quality of sleep was observed in both placebo (62%) and active (65%) group (p = 0.52). The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91). The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle. clinical trials.gov:NCT00484497.

Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)

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Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun Margrethe

2010-01-01

AND DESIGN: The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure =140 mm......Hg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway...

Specific music therapy techniques in the treatment of primary headache disorders in adolescents: a randomized attention-placebo-controlled trial.

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Koenig, Julian; Oelkers-Ax, Rieke; Kaess, Michael; Parzer, Peter; Lenzen, Christoph; Hillecke, Thomas Karl; Resch, Franz

2013-10-01

Migraine and tension-type headache have a high prevalence in children and adolescents. In addition to common pharmacologic and nonpharmacologic interventions, music therapy has been shown to be efficient in the prophylaxis of pediatric migraine. This study aimed to assess the efficacy of specific music therapy techniques in the treatment of adolescents with primary headache (tension-type headache and migraine). A prospective, randomized, attention-placebo-controlled parallel group trial was conducted. Following an 8-week baseline, patients were randomized to either music therapy (n = 40) or a rhythm pedagogic program (n = 38) designed as an "attention placebo" over 6 sessions within 8 weeks. Reduction of both headache frequency and intensity after treatment (8-week postline) as well as 6 months after treatment were taken as the efficacy variables. Treatments were delivered in equal dose and frequency by the same group of therapists. Data analysis of subjects completing the protocol showed that neither treatment was superior to the other at any point of measurement (posttreatment and follow-up). Intention-to-treat analysis revealed no impact of drop-out on these results. Both groups showed a moderate mean reduction of headache frequency posttreatment of about 20%, but only small numbers of responders (50% frequency reduction). Follow-up data showed no significant deteriorations or improvements. This article presents a randomized placebo-controlled trial on music therapy in the treatment of adolescents with frequent primary headache. Music therapy is not superior to an attention placebo within this study. These results draw attention to the need of providing adequate controls within therapeutic trials in the treatment of pain. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Electroacupuncture Versus Gabapentin for Hot Flashes Among Breast Cancer Survivors: A Randomized Placebo-Controlled Trial

Science.gov (United States)

Mao, Jun J.; Bowman, Marjorie A.; Xie, Sharon X.; Bruner, Deborah; DeMichele, Angela; Farrar, John T.

2015-01-01

Purpose Hot flashes are a common and debilitating symptom among survivors of breast cancer. This study aimed at evaluating the effects of electroacupuncture (EA) versus gabapentin (GP) for hot flashes among survivors of breast cancer, with a specific focus on the placebo and nocebo effects. Patients and Methods We conducted a randomized controlled trial involving 120 survivors of breast cancer experiencing bothersome hot flashes twice per day or greater. Participants were randomly assigned to receive 8 weeks of EA or GP once per day with validated placebo controls (sham acupuncture [SA] or placebo pills [PPs]). The primary end point was change in the hot flash composite score (HFCS) between SA and PP at week 8, with secondary end points including group comparisons and additional evaluation at week 24 for durability of treatment effects. Results By week 8, SA produced significantly greater reduction in HFCS than did PP (−2.39; 95% CI, −4.60 to −0.17). Among all treatment groups, the mean reduction in HFCS was greatest in the EA group, followed by SA, GP, and PP (−7.4 v −5.9 v −5.2 v −3.4; P = < .001). The pill groups had more treatment-related adverse events than did the acupuncture groups: GP (39.3%), PP (20.0%), EA (16.7%), and SA (3.1%), with P = .005. By week 24, HFCS reduction was greatest in the EA group, followed by SA, PP, and GP (−8.5 v −6.1 v −4.6 v −2.8; P = .002). Conclusion Acupuncture produced larger placebo and smaller nocebo effects than did pills for the treatment of hot flashes. EA may be more effective than GP, with fewer adverse effects for managing hot flashes among breast cancer survivors; however, these preliminary findings need to be confirmed in larger randomized controlled trials with long-term follow-up. PMID:26304905

A randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision

DEFF Research Database (Denmark)

Ågren, Magnus S.; Ostenfeld, Ulla; Kallehave, Finn Lasse

2006-01-01

The purpose of this randomized, double-blind, placebo-controlled multicenter trial was to compare topical zinc oxide with placebo mesh on secondary healing pilonidal wounds. Sixty-four (53 men) consecutive patients, aged 17-60 years, were centrally randomized to either treatment with 3% zinc oxide...... (n = 33) or placebo (n = 31) by concealed allocation. Patients were followed with strict recording of beneficial and harmful effects including masked assessment of time to complete wound closure. Analysis was carried out on an intention-to-treat basis. Median healing times were 54 days (interquartile...... range 42-71 days) for the zinc and 62 days (55-82 days) for the placebo group (p = 0.32). Topical zinc oxide increased (p placebo...

"I assumed that one was a placebo": exploring the consent process in a sham controlled acupressure trial.

Science.gov (United States)

Hughes, John Gareth; Russell, Wanda; Breckons, Matthew; Richardson, Janet; Lloyd-Williams, Mari; Molassiotis, Alex

2014-10-01

In clinical trials where participants are likely to be able to distinguish between true and sham interventions, informing participants that they may receive a sham intervention increases the likelihood of participants 'breaking the blind' and invalidating trial findings. The present study explored participants' perceptions of the consent process in a sham controlled acupressure trial which did not explicitly indicate participants may receive a sham intervention. Nested qualitative study within a randomised sham controlled trial of acupressure wristbands for chemotherapy-related nausea. Convenience sample of 26 patients participated in semi-structured interviews. Interviews were audio-recorded and transcribed verbatim. Transcripts analysed thematically using framework analysis. Study conducted within three geographical sites in the UK: Manchester, Liverpool, and Plymouth. All participants indicated that they believed they were fully informed when providing written consent to participate in the trial. Participants' perceived it was acceptable to employ a sham intervention within the trial of acupressure wristbands without informing potential participants that they may receive a sham treatment. Despite the fact that participants were not informed that one of the treatment arms was a sham intervention the majority indicated they assumed one of the treatment arms would be placebo. Many trials of acupuncture and acupressure do not inform participants they may receive a sham intervention. The current study indicates patients' perceive this approach to the consent process as acceptable. However, the fact participants assume one treatment may be placebo threatens the methodological basis for utilising this approach to the consent process. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of enzyme-potentiated desensitization in the treatment of pollinosis: a double-blind placebo-controlled trial.

Science.gov (United States)

Astarita, C; Scala, G; Sproviero, S; Franzese, A

1996-01-01

Several controlled clinical trials have shown that specific immunotherapy (SIT) using incremental injections of allergens can be effective in the treatment of allergic rhinitis and asthma. Nevertheless, the risk of side effects have led to some recommended limitations of SIT. Enzyme-potentiated desensitization (EPD) is a proposed method for immunotherapy with very low doses of mixed allergens plus beta-glucuronidase enzyme, for which irrelevant or no side effects have been claimed. The aim of this study was to determine the clinical efficacy of EPD in the treatment of pollinosis. A double-blind placebo-controlled trial of EPD among 20 patients sensitive to Parietaria and grass pollen was performed. All patients recorded daily symptom scores for nine months following a single intradermal injection of EPD or buffered saline received in February. Symptoms recorded were nasal itching and obstruction, sneezing, rhinorrhea, itchy eyes and excessive tear production. Moreover, total and specific lgE were measured and CD3+, CD4+ and CD8+ peripheral blood lymphocytes were counted at different times. In the same period, ten additional subjects, with an allergic clinical profile similar to the subjects admitted to the double-blind trial, were studied in an open clinical trial in order to evaluate the effects of EPD without enzyme using a mixture of allergens. Symptom scores were higher in the placebo group (p < 0.001), with a similar level of significance for both global symptom score and for each individual symptom. Active-treated patients had a significant post-treatment increase in the mean percentage of T-CD8+ peripheral blood cells and a significant post-seasonal decrease in the mean percentage of Parietaria specific lgE. On the contrary, placebo-treated patients had a borderline significant post-seasonal decrease in the mean percentage of CD8+ circulating cells and a significant seasonal increase in the mean percentage of Parietaria specific lgE with no significant post

Test Equality between Three Treatments under an Incomplete Block Crossover Design.

Science.gov (United States)

Lui, Kung-Jong

2015-01-01

Under a random effects linear additive risk model, we compare two experimental treatments with a placebo in continuous data under an incomplete block crossover trial. We develop three test procedures for simultaneously testing equality between two experimental treatments and a placebo, as well as interval estimators for the mean difference between treatments. We apply Monte Carlo simulations to evaluate the performance of these test procedures and interval estimators in a variety of situations. We note that the bivariate test procedure accounting for the dependence structure based on the F-test is preferable to the other two procedures when there is only one of the two experimental treatments has a non-zero effect vs. the placebo. We note further that when the effects of the two experimental treatments vs. a placebo are in the same relative directions and are approximately of equal magnitude, the summary test procedure based on a simple average of two weighted-least-squares (WLS) estimators can outperform the other two procedures with respect to power. When one of the two experimental treatments has a relatively large effect vs. the placebo, the univariate test procedure with using Bonferroni's equality can be still of use. Finally, we use the data about the forced expiratory volume in 1 s (FEV1) readings taken from a double-blind crossover trial comparing two different doses of formoterol with a placebo to illustrate the use of test procedures and interval estimators proposed here.

A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.

Science.gov (United States)

Wilens, Timothy E; Robertson, Brigitte; Sikirica, Vanja; Harper, Linda; Young, Joel L; Bloomfield, Ralph; Lyne, Andrew; Rynkowski, Gail; Cutler, Andrew J

2015-11-01

Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD. This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13. A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported. Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132. Copyright © 2015. Published by Elsevier Inc.

NMDA receptor antagonists interventions in schizophrenia: Meta-analysis of randomized, placebo-controlled trials.

Science.gov (United States)

Kishi, Taro; Iwata, Nakao

2013-09-01

We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results were across 8 studies and 406 patients (85.5% schizophrenia related disorder and 14.5% bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD = -0.25, CI = -0.72, 0.23, p = 0.31, N = 6, n = 347), positive symptoms (SMD = -0.20, CI = -0.70, 0.31, p = 0.44, N = 4, n = 205), and negative symptoms (SMD = -0.69, CI = -1.65, 0.27, p = 0.16, N = 4, n = 205), and Clinical Global Impression Severity scale (SMD = -0.27, CI = -1.20, 0.65, p = 0.56, N = 3, n = 177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR = 1.23, CI = 0.89-1.70, p = 0.20, N = 8, n = 396, side effects: RR = 1.86, CI = 0.84-4.13, p = 0.13, N = 6, n = 359, inefficacy/worsening psychosis: RR = 0.70, CI = 0.20-2.38, p = 0.56, N = 7, n = 380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD = -0.77, CI = -1.27, -0.28, p = 0.002, N = 3, n = 71). While NMDAR-ANTs caused weight loss compared with placebo (SMD = -0.42, CI = -0.73, -0.11, p = 0.008, N = 3, n = 165), amantadine caused more frequent insomnia than placebo (RR = 3.83, CI = 1.41-10.38, p = 0.008, NNH = 9, p = 0.002, N = 2, n = 147). Our results indicate that NMDAR-ANTs as adjunctive therapy may improve

A Randomized Double-blind, Placebo Controlled Trial of Venlafaxine-Extended Release for Co-occurring Cannabis Dependence and Depressive Disorders

Science.gov (United States)

Levin, Frances R.; Mariani, John; Brooks, Daniel J.; Pavlicova, Martina; Nunes, Edward V.; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A.; Carpenter, Kenneth M.

2013-01-01

Aim To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. Design This was a randomized, 12 week, double-blind, placebo-controlled trial of outpatients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. Settings The trial was conducted at two university research centers in the United States. Participants One hundred and three cannabis dependent adults participated in the trial. Measurements The primary outcome measures were 1) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and 2) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. Findings The proportion of patients achieving a clinically significant mood improvement [50% decrease in Hamilton Depression score from baseline] was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (X12=0.48, p-value= 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (X12=7.46, p-valuemarijuana use in the placebo group (F1,179=30.49, p-valuedepressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. PMID:23297841

Sono-electro-magnetic therapy for treating chronic pelvic pain syndrome in men: a randomized, placebo-controlled, double-blind trial.

Science.gov (United States)

Kessler, Thomas M; Mordasini, Livio; Weisstanner, Christian; Jüni, Peter; da Costa, Bruno R; Wiest, Roland; Thalmann, George N

2014-01-01

To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was -3.1 points (95% CI -6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks -1.6, 95% CI -2.8 to -0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score -8.3, 95% CI -14.5 to 2.6) than in patients with a longer symptom duration (-0.8, 95% CI -4.6 to 3.1; p for interaction = 0.023). Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. ClinicalTrials.gov NCT00688506.

Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen

NARCIS (Netherlands)

Vranken, J. H.; Dijkgraaf, M. G. W.; Kruis, M. R.; van der Vegt, M. H.; Hollmann, M. W.; Heesen, M.

2008-01-01

The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on

The effect of benzocaine and ketoprofen gels on pain during fixed orthodontic appliance treatment: a randomised, double-blind, crossover trial.

Science.gov (United States)

Eslamian, Ladan; Borzabadi-Farahani, Ali; Gholami, Hadi

2016-05-01

To compare the analgesic effect of topical benzocaine (5%) and ketoprofen (1.60 mg/mL) after 2 mm activation of 7 mm long delta loops used for maxillary en-masse orthodontic space closure. Twenty patients (seven males, 13 females, 15-25 years of age, mean age of 19.5 years) participated in a randomised crossover, double-blind trial. After appliance activation, participants were instructed to use analgesic gels and record pain perception at 2, 6, 24 hours and 2, 3 and 7 days (at 18.00 hrs), using a visual analogue scale ruler (VAS, 0-4). Each patient received all three gels (benzocaine, ketoprofen, and a control (placebo)) randomly, but at three different appliance activation visits following a wash-over gap of one month. After the first day, the patients were instructed to repeat gel application twice a day at 10:00 and 18:00 hrs for three days. The recorded pain scores were subjected to non-parametric analysis. The highest pain was recorded at 2 and 6 hours. Pain scores were significantly different between the three groups (Kruskal-Wallis test, p 0.05). A significant pain reduction was observed following the use of ketoprofen when tested against a control gel (placebo). The highest pain scores were experienced in patients administered the placebo and the lowest scores in patients who applied ketoprofen gel. Benzocaine had an effect mid-way between ketoprofen and the placebo. The highest pain scores were recorded 2 hours following force application, which decreased to the lowest scores after 7 days.

Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial.

Science.gov (United States)

Furyk, Jeremy S; Chu, Kevin; Banks, Colin; Greenslade, Jaimi; Keijzers, Gerben; Thom, Ogilvie; Torpie, Tom; Dux, Carl; Narula, Rajan

2016-01-01

We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter. This was a randomized, double-blind, placebo-controlled, multicenter trial of adult participants with calculus on computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion. There were 403 patients randomized, 81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95% confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95% confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was no difference in urologic interventions, time to self-reported stone passage, pain, or analgesia requirements. Adverse events were generally mild and did not differ between groups. We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Pozzoni, Pietro; Riva, Alessia; Bellatorre, Alessandro Giacco; Amigoni, Maria; Redaelli, Elena; Ronchetti, Anna; Stefani, Mariangela; Tironi, Rosangela; Molteni, Edoardo Ennio; Conte, Dario; Casazza, Giovanni; Colli, Agostino

2012-06-01

Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients. A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment. Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

Science.gov (United States)

Calabrese, C; Tosco, A; Abete, P; Carnovale, V; Basile, C; Magliocca, A; Quattrucci, S; De Sanctis, S; Alatri, F; Mazzarella, G; De Pietro, L; Turino, C; Melillo, E; Buonpensiero, P; Di Pasqua, A; Raia, V

2015-03-01

In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

The effect of almonds on inflammation and oxidative stress in Chinese patients with type 2 diabetes mellitus: a randomized crossover controlled feeding trial

Science.gov (United States)

Almond consumption is associated with ameliorations in obesity, hyperlipidemia, hypertension, and hyperglycemia. The hypothesis of this 12-wk randomized, crossover, controlled feeding trial was that almond consumption would ameliorate inflammation and oxidative stress in Chinese patients with type 2...

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

NARCIS (Netherlands)

Lawlor, B.; Kennelly, S.; O'Dwyer, S.; Cregg, F.; Walsh, C.; Coen, R.; Kenny, R.A.; Howard, R.; Murphy, C.; Adams, J.; Daly, L.; Segurado, R.; Gaynor, S.; Crawford, F.; Mullan, M.; Lucca, U.; Banzi, R.; Pasquier, F.; Breuilh, L.; Riepe, M.; Kalman, J.; Wallin, A.; Borjesson, A.; Molloy, W.; Tsolaki, M.; Olde Rikkert, M.G.M.

2014-01-01

INTRODUCTION: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82

Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial.

Science.gov (United States)

Morgan, Annette; Stevens, John

2010-07-01

The objective of this study was to investigate the effectiveness of Bacopa monnieri Linn. for improvement of memory performance in healthy older persons. This was a randomized, double-blind, placebo-controlled trial. The trial took place in Lismore, NSW, Australia between February and July 2005. Ninety-eight (98) healthy participants over 55 years of age were recruited from the general population. Participants were randomized to receive an extract of Bacopa monnieri called BacoMind(TM) (Natural Remedies Pvt. Ltd.), 300 mg/day, or an identical placebo. Following screening, neuropsychologic and subjective memory assessments were performed at baseline and at 12 weeks. Audioverbal and visual memory performance were measured by the Rey Auditory Verbal Learning Test (AVLT), the Rey-Osterrieth Complex Figure Test (CFT), and the Reitan Trail Making Test (TMT). Subjective memory performance was measured by the Memory Complaint Questionnaire (MAC-Q). One hundred and thirty-six (136) subjects volunteered; 103 met entry criteria, 98 commenced, and 81 completed the trial. Bacopa significantly improved verbal learning, memory acquisition, and delayed recall as measured by the AVLT: trial a4 (p = 0.000), trial a5 (p = 0.016); trial a6 (p = 0.000); trial a7 (delayed recall) (p = 0.001); total learning (p = 0.011); and retroactive interference (p = 0.048). CFT, MAC-Q, and TMT scores improved but group differences were not significant. Bacopa versus placebo caused gastrointestinal tract (GIT) side-effects. Bacopa significantly improved memory acquisition and retention in healthy older Australians. This concurs with previous findings and traditional use. Bacopa caused GIT side-effects of increased stool frequency, abdominal cramps, and nausea.

Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

Science.gov (United States)

Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

2014-01-01

Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here ‘BZD’) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. PMID:24286360

Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial.

Directory of Open Access Journals (Sweden)

Steven F L van Lelyveld

Full Text Available The immunomodulatory effects of the CCR5-antagonist maraviroc might be beneficial in patients with a suboptimal immunological response, but results of different cART (combination antiretroviral therapy intensification studies are conflicting. Therefore, we performed a 48-week placebo-controlled trial to determine the effect of maraviroc intensification on CD4+ T-cell counts and immune activation in these patients.Double-blind, placebo-controlled, randomized trial.Major inclusion criteria were 1. CD4+ T-cell count <350 cells/μL while at least two years on cART or CD4+ T-cell count <200 cells/μL while at least one year on cART, and 2. viral suppression for at least the previous 6 months. HIV-infected patients were randomized to add maraviroc (41 patients or placebo (44 patients to their cART regimen for 48 weeks. Changes in CD4+ T-cell counts (primary endpoint and other immunological parameters were modeled using linear mixed effects models.No significant differences for the modelled increase in CD4+ T-cell count (placebo 15.3 CD4+ T cells/μL (95% confidence interval (CI [1.0, 29.5] versus maraviroc arm 22.9 CD4+ T cells/μL (95% CI [7.4, 38.5] p = 0.51 or alterations in the expression of markers for T-cell activation, proliferation and microbial translocation were found between the arms. However, maraviroc intensification did increase the percentage of CCR5 expressing CD4+ and CD8+ T-cells, and the plasma levels of the CCR5 ligand MIP-1β. In contrast, the percentage of ex-vivo apoptotic CD8+ and CD4+ T-cells decreased in the maraviroc arm.Maraviroc intensification of cART did not increase CD4+ T-cell restoration or decrease immune activation as compared to placebo. However, ex-vivo T-cell apoptosis was decreased in the maraviroc arm.ClinicalTrials.gov NCT00875368.

A Randomized, Double-Blind Placebo Controlled Trial of Balapiravir, a Polymerase Inhibitor, in Adult Dengue Patients

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Nguyen, Nguyet Minh; Tran, Chau Nguyen Bich; Phung, Lam Khanh; Duong, Kien Thi Hue; Huynh, Huy le Anh; Farrar, Jeremy; Nguyen, Quyen Than Ha; Tran, Hien Tinh; Nguyen, Chau Van Vinh; Merson, Laura; Hoang, Long Truong; Hibberd, Martin L.; Aw, Pauline P. K.; Wilm, Andreas; Nagarajan, Niranjan; Nguyen, Dung Thi; Pham, Mai Phuong; Nguyen, Truong Thanh; Javanbakht, Hassan; Klumpp, Klaus; Hammond, Janet; Petric, Rosemary; Wolbers, Marcel; Nguyen, Chinh Tran; Simmons, Cameron P.

2013-01-01

Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576. PMID:22807519

An evaluation of the hypolipidemic effect of an extract of Hibiscus Sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial

Science.gov (United States)

2010-01-01

Background Hibiscus sabdariffa is used regularly in folk medicine to treat various conditions. Methods The study was a double blind, placebo controlled, randomized trial. Sixty subjects with serum LDL values in the range of 130-190 mg/dl and with no history of coronary heart disease were randomized into experimental and placebo groups. The experimental group received 1 gm of the extract for 90 days while the placebo received a similar amount of maltodextrin in addition to dietary and physical activity advice for the control of their blood lipids. Anthropometry, blood biochemistry, dietary and physical activity were assessed at baseline, day 45 and day 90. Results While body weight, serum LDL cholesterol and triglyceride levels decreased in both groups, there were no significant differences between the experimental and placebo group. Conclusions It is likely that the observed effects were as a result of the patients following the standard dietary and physical activity advice. At a dose of 1 gm/day, hibiscus sabdariffa leaf extract did not appear to have a blood lipid lowering effect. Trial Registration REFCTRI2009000472 PMID:20553629

An evaluation of the hypolipidemic effect of an extract of Hibiscus Sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial

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R Rajendran

2010-06-01

Full Text Available Abstract Background Hibiscus sabdariffa is used regularly in folk medicine to treat various conditions. Methods The study was a double blind, placebo controlled, randomized trial. Sixty subjects with serum LDL values in the range of 130-190 mg/dl and with no history of coronary heart disease were randomized into experimental and placebo groups. The experimental group received 1 gm of the extract for 90 days while the placebo received a similar amount of maltodextrin in addition to dietary and physical activity advice for the control of their blood lipids. Anthropometry, blood biochemistry, dietary and physical activity were assessed at baseline, day 45 and day 90. Results While body weight, serum LDL cholesterol and triglyceride levels decreased in both groups, there were no significant differences between the experimental and placebo group. Conclusions It is likely that the observed effects were as a result of the patients following the standard dietary and physical activity advice. At a dose of 1 gm/day, hibiscus sabdariffa leaf extract did not appear to have a blood lipid lowering effect. Trial Registration REFCTRI2009000472

Randomized, Double-Blind, Placebo-Controlled Trial of N-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder.

Science.gov (United States)

Costa, Daniel L C; Diniz, Juliana B; Requena, Guaraci; Joaquim, Marinês A; Pittenger, Christopher; Bloch, Michael H; Miguel, Euripedes C; Shavitt, Roseli G

2017-07-01

To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD). We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18-65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014). The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance with repeated measures. Secondary outcomes were the severity scores for anxiety, depression, specific OCD symptom dimensions, and insight. Both groups showed a significant reduction of baseline Y-BOCS scores at week 16: the NAC group had a reduction of 4.3 points (25.6 to 21.3), compared with 3.0 points (24.8 to 21.8) for the placebo group. However, there were no significant differences between groups (P = .92). Adding NAC was superior to placebo in reducing anxiety symptoms (P = .02), but not depression severity or specific OCD symptom dimensions. In general, NAC was well tolerated, despite abdominal pain being more frequently reported in the NAC group (n [%]: NAC = 9 [60.0], placebo = 2 [13.3]; P < .01). Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatment-resistant OCD adults. Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients. ClinicalTrials.gov identifier: NCT01555970. © Copyright 2017 Physicians Postgraduate Press, Inc.

Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain[ISRCTN83088383

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Nadeson Raymond

2005-04-01

Full Text Available Abstract Background Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. Methods Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. Results The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. Conclusion A serum concentration of ketamine that did not alter

A randomised placebo-controlled trial to differentiate the acute cognitive and mood effects of chlorogenic acid from decaffeinated coffee.

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David A Camfield

Full Text Available In the current study, sixty healthy older adults aged 50 years or older, and who were light to moderate coffee drinkers, were administered 6g of a decaffeinated green coffee blend (NESCAFÉ Green Blend coffee; GB or 540mg pure chlorogenic acids (CGA or placebo in a double-blind acute cross-over design, with cognitive and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary outcome measure was accuracy in Rapid Visual Information Processing (RVIP. Secondary cognitive outcome measures included RVIP reaction time as well as Inspection time (IT, Jensen Box decision/reaction times, serial subtraction and N-Back working memory. Secondary mood measures included Bond-Lader and caffeine Research visual analogue scales (VAS. No significant treatment effects were found for the primary outcome measure, although significant effects were found amongst secondary measures. Overall, CGA in isolation was not found to significantly improve cognitive function relative to placebo whereas the GB was found to improve sustained attention as measured by the N-Back task in comparison to placebo overall (t=2.45,p=.05, as well as decision time on a 2-choice reaction time task (Jensen box in comparison to placebo at 40 minutes post-dose (t=2.45,p=.05. Similarly, GB was found to improve alertness on both the Bond-Lader at 120 minutes relative to CGA (t=2.86, p=0.02 and the caffeine Research VAS relative to CGA (t=3.09, p=0.009 and placebo (t=2.75,p=0.02 at 120 minutes post-dose. Both the GB and CGA were also found to significantly improve symptoms of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04 respectively, whilst there was a trend towards a reduction in jitteriness with GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and t=2.20,p=0.06 respectively. These findings suggest that the improvements in mood observed with GB, but not the improvements in cognitive function, are likely to some extent to be

Are child and adolescent responses to placebo higher in major depression than in anxiety disorders? A systematic review of placebo-controlled trials.

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David Cohen

Full Text Available BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD, obsessive compulsive disorder (OCD and other anxiety disorders (AD-non-OCD. METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD, age (adolescent vs. child, and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms. As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002. Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.

Effects of sertindole on cognition in clozapine-treated schizophrenia patients - a double-blinded, randomized, placebo-controlled trial

DEFF Research Database (Denmark)

Nielsen, R E; Levander, S; Nielsen, Jimmi

Nielsen RE, Levander S, Thode D, Nielsen J. Effects of sertindole on cognition in clozapine-treated schizophrenia patients. Objective:  To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial....... Method:  A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine. Results:  Participants displayed substantial cognitive deficits......, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative...

The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials

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Papadopoulos George

2007-10-01

Full Text Available Abstract Background Topiramate is approved for the prophylaxis (prevention of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ scores versus placebo (p Methods Mean MSQ and Medical Outcome Study Short Form 36 (SF-36 change scores (baseline to each double-blind assessment point were calculated for pooled intent-to-treat (ITT patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: Results Of 756 patients (mean age 39.8 years, 86% female, 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p Conclusion Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a ≥ 50% migraine frequency reduction.

The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model- A Randomized, Placebo-Controlled Trial

DEFF Research Database (Denmark)

Larsen, Isabelle M; Drewes, Asbjørn M; Olesen, Anne E

2018-01-01

should be low. We hypothesized that anti-allodynic and anti-hyperalgesic effects of Diclometh could be demonstrated in a human experimental pain model, and that Diclometh would be safe to administer. Thus, the aims were: 1) To compare two doses of Diclometh versus placebo; 2) To assess the safety profile...... of Diclometh. The study was a cross-over, randomized, double-blind, placebo-controlled comparison of two doses of Diclometh gel (0.1% and 0.2%) administered topically in healthy participants. Nerve growth factor (NGF) and capsaicin intradermal injections were used as human pain models. Pressure stimulation...... of anti-allodynic effect of Diclometh 0.2% was found. Additionally, it was demonstrated that Diclometh was safe to use. This article is protected by copyright. All rights reserved....

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study.

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Enseleit, Frank; Sudano, Isabella; Périat, Daniel; Winnik, Stephan; Wolfrum, Mathias; Flammer, Andreas J; Fröhlich, Georg M; Kaiser, Priska; Hirt, Astrid; Haile, Sarah R; Krasniqi, Nazmi; Matter, Christian M; Uhlenhut, Klaus; Högger, Petra; Neidhart, Michel; Lüscher, Thomas F; Ruschitzka, Frank; Noll, Georg

2012-07-01

Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo-controlled, randomized, crossover study with four ABPM.

Science.gov (United States)

Puig, J G; Calvo, C; Luurila, O; Luurila, H; Sulosaari, S; Strandberg, A; Ghezzi, C

2007-12-01

This double-blind, placebo-controlled, four-way balanced design crossover study included hypertensive patients aged 60-85 years with mean office-measured sitting systolic blood pressure (SBP) 160-179 mm Hg and daytime SBP > or =135 mm Hg. After a 2-week run-in period, during which previous medications were discontinued, each patient received the following four treatments in randomized order for 4 weeks each: lercanidipine 10 mg (L), enalapril 20 mg (E), lercanidipine 10 mg plus enalapril 20 mg (L/E) and placebo (P). At the end of each treatment period, office trough blood pressure (BP) was measured and a 24-h Ambulatory Blood Pressure Monitoring (ABPM) was performed. Seventy-five patients (mean age 66 years, office BP 168/92 mm Hg, daytime SBP 151 mm Hg) were randomized and 62 completed the study with four valid post-baseline ABPMs. The administration of P, L, E and L/E was associated with a mean 24-h SBP of 144, 137, 133 and 127 mm Hg, respectively. All active treatments significantly reduced the mean 24-h SBP in comparison with placebo, but L/E was significantly more effective than L and E alone. Similarly, office SBP was significantly more reduced with L/E (-16.9 mm Hg) than with L (-5.0 mm Hg) or E (-5.9 mm Hg). A BP <140/90 mm Hg was recorded in 18% of patients with L, 19% with E and 45% with L/E. Two patients on P and two on L/E were withdrawn from the study due to adverse events. In conclusion, combination therapy with L/E has additive antihypertensive effects on both ambulatory and office BP in elderly patients and is well tolerated.

A randomised, double blind, placebo-controlled, multi-centric parallel arm trial to assess the effects of homoeopathic medicines on chronic rhinosinusitis

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Raj K Manchanda

2014-01-01

Full Text Available Background: Chronic rhinosinusitis (CRS is one of the most common illnesses interfering with patient′s quality of life and work. Observational studies conducted by the Council indicate positive outcome. This protocol has been developed to ascertain the usefulness of homoeopathic intervention in comparison with control group in a randomised control setting. Objectives: Primary objective is to evaluate the changes in TSS (Total Symptoms Score and SNOT-22 (Sino-nasal Outcome Test-22 within the two groups of the study (Homoeopathy + Placebo. Secondary objective is to evaluate changes in SNOT-22 at end of the trial, changes in Lund and Mackay staging of CT scan, rhinoscopy grading, absolute eosinophil count, global assessment by investigator and patient, and number of acute exacerbations of CRS (for frequency, duration and intensity as per TSS scale compared to placebo. Methods/Design: This is a randomised double blind, placebo-controlled, multi-centric parallel arm trial of 6 months (three months treatment and three months observation period with 14 days run-in period. The primary outcome is a composite of the changes in the TSS and SNOT-22 over 3 months from baseline with area under the curve and changes over 3 months in the Sinus Nasal Outcome Test 22 (SNOT-22 from baseline. Prescription shall be made as per the homoeopathic principles. Efficacy data will be analysed in the intention-to-treat population. Discussion: This trial will help to evaluate the efficacy of homoeopathic individualised treatment using LM-potencies versus placebo in patients suffering from CRS as per the homoeopathic dictum.

A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children

OpenAIRE

Kambiz Eftekhari; Zahra Vahedi; Mojtaba Kamali Aghdam; Diana Noemi Diaz

2015-01-01

Background: Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it. Objectives: The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain. Patients and Methods: This study was a randomized double-blind placebo-controlled trial. Children aged 4 to ...

A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders.

Science.gov (United States)

Levin, Frances R; Mariani, John; Brooks, Daniel J; Pavlicova, Martina; Nunes, Edward V; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A; Carpenter, Kenneth M

2013-06-01

To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. The trial was conducted at two university research centers in the United States. One hundred and three cannabis-dependent adults participated in the trial. The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2)  = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2)  = 7.46, P marijuana use in the placebo group (F1,179  = 30.49, P depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. © 2013 Society for the Study of Addiction.

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

OpenAIRE

Villar-Garc?a, Judit; G?erri-Fern?ndez, Robert; Moya, Andr?s; Gonz?lez, Alicia; Hern?ndez, Juan J.; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P.; Artacho, Alejandro; D?Auria, Giuseppe; Knobel, Hernando

2017-01-01

Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly ...

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: a multicenter randomized placebo controlled trial.

Science.gov (United States)

Visser, Laura; de Boer, Marjon A; de Groot, Christianne J M; Nijman, Tobias A J; Hemels, Marieke A C; Bloemenkamp, Kitty W M; Bosmans, Judith E; Kok, Marjolein; van Laar, Judith O; Sueters, Marieke; Scheepers, Hubertina; van Drongelen, Joris; Franssen, Maureen T M; Sikkema, J Marko; Duvekot, Hans J J; Bekker, Mireille N; van der Post, Joris A M; Naaktgeboren, Christiana; Mol, Ben W J; Oudijk, Martijn A

2017-07-14

Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial.

Science.gov (United States)

Gerami, Hooshang; Saberi, Alia; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

2012-01-01

It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus. In a randomized double-blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tinnitus severity index (TSI) were measured in all subjects in the beginning and at the end of the 8(th) and 12(th) weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test. Among 51 participants who completed the trial course (28 men, 23 women), carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28). Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity.

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

Science.gov (United States)

de Ridder, Inger R; den Hertog, Heleen M; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; van Tuijl, Jordie H; Jansen, Ben P W; Van den Berg-Vos, Renske M; Vermeij, Frederique; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2017-04-01

Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. URL: http://www.trialregister.nl. Unique identifier: NTR2365. © 2017 American Heart Association, Inc.

Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial.

Science.gov (United States)

van den Bogaard, Bas; Draijer, Richard; Westerhof, Berend E; van den Meiracker, Anton H; van Montfrans, Gert A; van den Born, Bert-Jan H

2010-11-01

Flavanol-rich cocoa products have been reported to lower blood pressure. It has been suggested that theobromine is partially responsible for this effect. We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure. In a double-blind, placebo-controlled 3-period crossover trial we assigned 42 healthy individuals (age 62±4.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg and low added cardiovascular risk to a random treatment sequence of dairy drinks containing placebo, flavanol-rich cocoa with natural dose consisting of 106 mg of theobromine, or theobromine-enriched flavanol-rich cocoa with 979 mg of theobromine. Treatment duration was 3 weeks with a 2-week washout. The primary outcome was the difference in 24-hour ambulatory systolic blood pressure between placebo and active treatment after 3 weeks. The difference in central systolic blood pressure between placebo and active treatment was a secondary outcome. Treatment with theobromine-enriched cocoa resulted in a mean±SE of 3.2±1.1 mm Hg higher 24-hour ambulatory systolic blood pressure compared with placebo (Ptheobromine-enriched cocoa, laboratory peripheral systolic blood pressure was not different from placebo, whereas central systolic blood pressure was 4.3±1.4 mm Hg lower (P=0.001). Natural dose theobromine cocoa did not significantly change either 24-hour ambulatory or central systolic blood pressure compared with placebo. In conclusion, theobromine-enriched cocoa significantly increased 24-hour ambulatory systolic blood pressure while lowering central systolic blood pressure.

Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.

Science.gov (United States)

Tarumi, Yoko; Wilson, Mitchell P; Szafran, Olga; Spooner, G Richard

2013-01-01

The stool softener docusate is widely used in the management of constipation in hospice patients. There is little experimental evidence to support this practice, and no randomized trials have been conducted in the hospice setting. To assess the efficacy of docusate in hospice patients. This was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. Patients were included if they were age 18 years or older, able to take oral medications, did not have a gastrointestinal stoma, and had a Palliative Performance Scale score of 20% or more. The primary outcome measures were stool frequency, volume, and consistency. Secondary outcomes were patient perceptions of bowel movements (difficulty and completeness of evacuation) and bowel-related interventions. A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were neither significant differences between the groups in stool frequency, volume, or consistency, nor in difficulty or completeness of evacuation. On the Bristol Stool Form Scale, more patients in the placebo group had Type 4 (smooth and soft) and Type 5 (soft blobs) stool, whereas in the docusate group, more had Type 3 (sausage like) and Type 6 (mushy) stool (P=0.01). There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate use should be considered on an individual basis. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial

DEFF Research Database (Denmark)

Sjolie, A.K.; Klein, R.; Porta, M.

2008-01-01

-group, placebo-controlled trial in 309 centres worldwide. We recruited normoalbuminuric, normotensive, or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to candesartan 16 mg once a day or placebo. After a month, the dose was doubled to 32 mg once per...... day. Investigators and patients were unaware of the treatment allocation status. Progression of retinopathy was the primary endpoint, and regression was a secondary endpoint. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00252694. FINDINGS: 1905...... or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05-1.30, p=0.003). Adverse events did not differ between the treatment groups. INTERPRETATION: Treatment with candesartan in type...

Dietary Supplementation with a Superoxide Dismutase-Melon Concentrate Reduces Stress, Physical and Mental Fatigue in Healthy People: A Randomised, Double-Blind, Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Julie Carillon

2014-06-01

Full Text Available Background: We aimed to investigate effects of superoxide dismutase (SOD-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. Methods: A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32 and placebo (n = 29 for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. Results: The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. Conclusion: SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. Trial registration: trial approved by the ethical committee of Poitiers (France, and the ClinicalTrials.gov Identifier is NCT01767922.

Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms.

Science.gov (United States)

Gerber, G S; Kuznetsov, D; Johnson, B C; Burstein, J D

2001-12-01

To assess the effects of saw palmetto on urinary symptoms, sexual function, and urinary flow rate in men with lower urinary tract symptoms using a double-blind, randomized, placebo-controlled trial. The eligible patients were 45 years of age or older and had an International Prostate Symptom Score of 8 or greater. After a 1-month placebo run-in period, 85 men were randomized to receive saw palmetto or placebo for 6 months. Patients were evaluated using the International Prostate Symptom Score, a sexual function questionnaire, and by measurement of the urinary flow rate. The mean symptom score decreased from 16.7 to 12.3 in the saw palmetto group compared with 15.8 to 13.6 in the placebo group (P = 0.038). The quality-of-life score improved to a greater degree in the saw palmetto group, but this difference was not statistically significant. No change occurred in the sexual function questionnaire results in either group. The peak flow rate increased by 1.0 mL/s and 1.4 mL/s in the saw palmetto and placebo groups, respectively (P = 0.73). Saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo. Saw palmetto had no measurable effect on the urinary flow rates. The mechanism by which saw palmetto improves urinary symptoms remains unknown.

Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

Science.gov (United States)

Ortiz, Justin R; Goswami, Doli; Lewis, Kristen D C; Sharmeen, Amina Tahia; Ahmed, Moshtaq; Rahman, Mustafizur; Rahman, Mohammed Z; Feser, Jodi; Neuzil, Kathleen M; Brooks, W Abdullah

2015-06-26

Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian

Memantine in frontotemporal lobar degeneration: A multicenter, randomised, double-blind, placebo-controlled trial

Science.gov (United States)

Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadi; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang-Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

2013-01-01

Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). Methods We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 Findings 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. Interpretation There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Funding Forest Research Institute PMID:23290598

Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.

Science.gov (United States)

Jacobs, Ian G; Finn, Judith C; Jelinek, George A; Oxer, Harry F; Thompson, Peter L

2011-09-01

There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest. We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC). A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2. Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A Randomized, Double-Blind, Placebo-Controlled Trial of Eszopiclone for the Treatment of Insomnia in Patients with Chronic Low Back Pain

Science.gov (United States)

Goforth, Harold W.; Preud'homme, Xavier A.; Krystal, Andrew D.

2014-01-01

Study Objectives: Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP. Design: Double-blind, placebo-controlled, parallel-group, 1-mo trial. Setting: Duke University Medical Center Outpatient Sleep Clinic. Patients: Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females). Interventions: Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day. Measurements and Results: ESZ significantly improved total sleep time (mean increase: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep. Conclusions: The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain. Trial Registration: clinicaltrials.gov identifier: NCT00365976 Citation: Goforth HW, Preud'homme XA, Krystal AD. A randomized, double-blind, placebo-controlled trial of eszopiclone

The antidepressant debate and the balanced placebo trial design: an ethical analysis.

Science.gov (United States)

Waring, Duff R

2008-12-01

There is ongoing debate about whether randomized, placebo-controlled trials under a double-blind have reliably established the pharmacological efficacy of antidepressants. Numerous meta-analyses of antidepressant efficacy trials, e.g., Kirsch et al. [Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. food and drug administration. Prevention and Treatment, 5, Article 23. (Retrieved July 19, 2007 from http://journals.apa.org/prevention/volume5)], have shown a modest drug-placebo difference but methodological problems with standard trial design preclude a definitive conclusion that this difference results from specific biological effects of antidepressants or the nonspecific factors that have not been adequately excluded. Standard trial design assumes the additivity thesis of pharmacological efficacy, being the assumption that the specific or "true" magnitude of the pharmacological effect is limited to the difference between the drug and placebo responses in a standard trial. If the drug effects are as small as these meta-analyses suggest, then their clinical effectiveness is questionable. If the drug effects are actually larger but masked by placebo effects, then the additivity thesis is not valid and we risk false negative results with standard trial design. Kirsch et al. propose an alternative, four arm balanced placebo trial design (BPTD) that can accurately test the additivity thesis. The BPTD uses antidepressants, active placebos and the intentional deception of research subjects. My focal question is whether the BPTD is ethically defensible. I will explore two objections that can be raised against it: 1) lying to BPTD research subjects violates their autonomy and exploits their illness and 2) the BPTD may not enable us to test the additivity thesis with accuracy, i.e., it may contribute to the masking of drug effects that it aims to avoid. I argue that these

Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.

LENUS (Irish Health Repository)

Phelan, Niamh

2012-02-01

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. OBJECTIVES: We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies. DESIGN: We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells. RESULTS: Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05). CONCLUSIONS: Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was

Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

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Sarris Jerome

2012-12-01

Full Text Available Abstract Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16, three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender. Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022 and enhanced mood (p=.027. The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin

Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial

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Ghoreishi Zohreh

2012-08-01

Full Text Available Abstract Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN. Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". Results Twenty one patients (70% of the group taking omega-3 fatty acid supplement (n = 30 did not develop PN while it was 40.7%( 11 patients in the placebo group(n = 27. A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88, p = 0.029. There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02, p = 0.054. Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life. Trial registration This trial was registered at ClinicalTrials.gov (NCT01049295

Topical sucralfate treatment of anal fistulotomy wounds: a randomized placebo-controlled trial.

Science.gov (United States)

Gupta, Pravin J; Heda, Purushottam S; Shrirao, Subhash A; Kalaskar, Surekha S

2011-06-01

Sucralfate is a cytoprotective agent which adheres to mucoproteins and forms a protective barrier at wound sites. In oral form it is a common ulcer medication, and as a topical preparation it has been used to treat a wide variety of wounds. The present study was designed to evaluate the effectiveness and safety of topical sucralfate in wound healing after anal fistulotomy. Double-blind, randomized controlled study comparing topical application of sucralfate or placebo. Private outpatient clinic specializing in anorectal disease in Nagpur, India. Patients with a wound length of at least 5 cm after low anal fistulotomy were eligible for the study. Patients were randomly assigned to receive ointment containing 7% sucralfate or a placebo ointment consisting of petroleum jelly. Patients were instructed to apply approximately 3 g of ointment to the wound twice daily after a sitz bath for 6 weeks or until the wound had healed. The wounds were examined by a blinded independent observer at 2, 4, and 6 weeks after the operation. The primary end point was the proportion of patients with wounds that had completely healed. Secondary end points included amount of mucosal covering (scored by the observer), adverse events, and postoperative pain (self-rated on a visual analog scale). Of 80 participants (29 women, 51 men; median age, 23 (range, 17-49) years), 76 participants completed the trial (sucralfate, 39; placebo, 37). At 6-week follow-up, complete wound healing was achieved in 37 patients (95%) in the sucralfate group and 27 patients (73%) in the placebo group (P = .009). Mucosal coverage of the wound was significantly greater with sucralfate than with placebo at each measurement point (P = .01). No adverse events were observed. Postoperative pain scores were significantly lower for sucralfate than for placebo at 2 and 4 weeks after the start of treatment. Wound tissue specimens were not available for morphological and ultrastructural analysis. The results of this study add

Dietary supplementation with a superoxide dismutase-melon concentrate reduces stress, physical and mental fatigue in healthy people: a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Carillon, Julie; Notin, Claire; Schmitt, Karine; Simoneau, Guy; Lacan, Dominique

2014-06-19

We aimed to investigate effects of superoxide dismutase (SOD)-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32) and placebo (n = 29) for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD) and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. trial approved by the ethical committee of Poitiers (France), and the ClinicalTrials.gov Identifier is NCT01767922.

A randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision

DEFF Research Database (Denmark)

Agren, Magnus S; Ostenfeld, Ulla; Kallehave, Finn

2006-01-01

The purpose of this randomized, double-blind, placebo-controlled multicenter trial was to compare topical zinc oxide with placebo mesh on secondary healing pilonidal wounds. Sixty-four (53 men) consecutive patients, aged 17-60 years, were centrally randomized to either treatment with 3% zinc oxide...... range 42-71 days) for the zinc and 62 days (55-82 days) for the placebo group (p = 0.32). Topical zinc oxide increased (p zinc levels to 1,540 (1,035-2,265) microM and decreased (p zinc oxide (n = 3) than placebo......-treated patients (n = 12) were prescribed postoperative antibiotics (p = 0.005). Serum-zinc levels increased (p Zinc oxide was not associated with increased pain by the visual analog scale, cellular...

Melatonin Improves Health Status and Sleep in Children With Idiopathic Chronic Sleep-Onset Insomnia: A Randomized Placebo-Controlled Trial

NARCIS (Netherlands)

Smits, M.G.; Stel, H.F. van; Heijden, K.B. van der; Meijer, A.M.; Coenen, A.M.L.; Kerkhof, G.A.

2003-01-01

Objective: To investigate the effect of melatonin treatment on health status and sleep in children with idiopathic sleep-onset insomnia. Method: A randomized, double-blind, placebo-controlled trial was conducted in a Dutch sleep center, involving 62 children, 6 to 12 years of age, who suffered more

Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: A randomized, placebo-controlled clinical trial

Science.gov (United States)

Moraska, Albert F.; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P.; Schmiege, Sarah J.; Mann, J. Douglas

2014-01-01

Objective Myofascial trigger points (MTrPs) are focal disruptions in skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type headache (TTH). The present study applied massage focused on MTrPs of subjects with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache pain. Methods Fifty-six subjects with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over six weeks, or to wait-list. Trigger point release (TPR) massage focused on MTrPs in cervical musculature. Headache pain (frequency, intensity and duration) was recorded in a daily headache diary. Additional outcome measures included self-report of perceived clinical change in headache pain and pressure-pain threshold (PPT) at MTrPs in the upper trapezius and sub-occipital muscles. Results From diary recordings, group differences across time were detected in headache frequency (p=0.026), but not for intensity or duration. Post hoc analysis indicated headache frequency decreased from baseline for both massage (pheadache pain for massage than placebo or wait-list groups (p=0.002). PPT improved in all muscles tested for massage only (all p'streatment of TTH, and 2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on headache that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention. PMID:25329141

A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state.

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Ashwin Patkar

Full Text Available OBJECTIVE: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD. METHODS: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE, while also meeting 2 or 3 (but not more nor less DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo. RESULTS: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038. Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036. Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms. CONCLUSIONS: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state. TRIAL REGISTRATION: Clinicaltrials.gov NCT00490542.

Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

DEFF Research Database (Denmark)

Juul, Anne Benedicte; Wetterslev, Jørn; Gluud, Christian

2006-01-01

Objectives To evaluate the long term effects of perioperative blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University...

Randomized, placebo-controlled, double-blind trial of Swedish snus for smoking reduction and cessation

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Nilsson Robert

2011-09-01

Full Text Available Abstract Background Epidemiological studies suggest that smokeless tobacco in the form of Swedish snus has been used by many smokers in Scandinavia to quit smoking, but the efficacy of snus has so far not been evaluated in controlled clinical trials. Methods We conducted a randomized, double-blind, placebo-controlled, clinical trial aimed at assessing the efficacy of snus to help adult cigarette smokers in Serbia to substantially reduce, and, eventually, completely stop smoking. The study enrolled 319 healthy smokers aged 20-65 years at two occupational health centers in Belgrade, Serbia. Most of them (81% expressed an interest to quit rather than just reduce their smoking. Study products were used ad libitum throughout the 48-week study period. The main study objective during the first 24 weeks was smoking reduction. The primary end-point was defined as a biologically verified reduction of ≥ 50% in the average number of smoked cigarettes per day during week 21-24 compared to baseline. During week 25-48 participants were actively instructed to stop smoking completely. Outcome measures of biologically verified, complete smoking cessation included 1-week point prevalence rates at clinical visits after 12, 24, 36, and 48 weeks, as well as 4-, 12- and 24-week continued cessation rates at the week 36 and 48 visits. Results At the week 24 visit, the proportion of participants who achieved the protocol definition of a ≥ 50% smoking reduction was similar in the two treatment groups. However, the proportion that reported more extreme reductions (≥ 75% was statistically significantly higher in the snus group than in the placebo group (p Conclusions Swedish snus could promote smoking cessation among smokers in Serbia, that is, in a cultural setting without traditional use of oral, smokeless tobacco. Trial registration www.clinicaltrials.gov, identifier: NCT00601042

Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial.

Science.gov (United States)

Pase, Matthew P; Scholey, Andrew B; Pipingas, Andrew; Kras, Marni; Nolidin, Karen; Gibbs, Amy; Wesnes, Keith; Stough, Con

2013-05-01

This study aimed to examine the acute and sub-chronic effects of cocoa polyphenols on cognition and mood. In a randomized, double-blind study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg or 0 mg of polyphenols (placebo) in a parallel-groups design. Participants consumed their assigned treatment once daily for 30 days. Cognition was measured with the Cognitive Drug Research system and self-rated mood with the Bond-Lader Visual Analogue Scale. Participants were tested at baseline, at 1, 2.5 and 4 h after a single acute dose and again after receiving 30 days of treatment. In total, 72 participants completed the trial. After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to placebo. Mood was unchanged by treatment acutely while cognition was unaffected by treatment at all time points. This randomized controlled trial is perhaps the first to demonstrate the positive effects of cocoa polyphenols on mood in healthy participants. This provides a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

Science.gov (United States)

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-12-01

The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. © 2014 The British Pharmacological Society.

Ankle manual therapy for individuals with post-acute ankle sprains: description of a randomized, placebo-controlled clinical trial

Directory of Open Access Journals (Sweden)

Fisher Beth E

2010-10-01

Full Text Available Abstract Background Ankle sprains are common within the general population and can result in prolonged disablement. Limited talocrural dorsiflexion range of motion (DF ROM is a common consequence of ankle sprain. Limited talocrural DF ROM may contribute to persistent symptoms, disability, and an elevated risk for re-injury. As a result, many health care practitioners use hands-on passive procedures with the intention of improving talocrural joint DF ROM in individuals following ankle sprains. Dosage of passive hands-on procedures involves a continuum of treatment speeds. Recent evidence suggests both slow- and fast-speed treatments may be effective to address disablement following ankle sprains. However, these interventions have yet to be longitudinally compared against a placebo study condition. Methods/Design We developed a randomized, placebo-controlled clinical trial designed to test the hypotheses that hands-on treatment procedures administered to individuals following ankle sprains during the post-acute injury period can improve short-, intermediate-, and long-term disablement, as well as reduce the risk for re-injury. Discussion This study is designed to measure the clinical effects of hands-on passive stretching treatment procedures directed to the talocrural joint that vary in treatment speed during the post-acute injury period, compared to hands-on placebo control intervention. Trial Registration http://www.clinicaltrials.gov identifier NCT00888498.

Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial.

Science.gov (United States)

Harris, Deborah L; Weston, Philip J; Signal, Matthew; Chase, J Geoffrey; Harding, Jane E

2013-12-21

Neonatal hypoglycaemia is common, and a preventable cause of brain damage. Dextrose gel is used to reverse hypoglycaemia in individuals with diabetes; however, little evidence exists for its use in babies. We aimed to assess whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. We undertook a randomised, double-blind, placebo-controlled trial at a tertiary centre in New Zealand between Dec 1, 2008, and Nov 31, 2010. Babies aged 35-42 weeks' gestation, younger than 48-h-old, and at risk of hypoglycaemia were randomly assigned (1:1), via computer-generated blocked randomisation, to 40% dextrose gel 200 mg/kg or placebo gel. Randomisation was stratified by maternal diabetes and birthweight. Group allocation was concealed from clinicians, families, and all study investigators. The primary outcome was treatment failure, defined as a blood glucose concentration of less than 2·6 mmol/L after two treatment attempts. Analysis was by intention to treat. The trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12608000623392. Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 [14%] vs 29 [24%]; relative risk 0·57, 95% CI 0·33-0·98; p=0·04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0·9 mmol/L. No other adverse events took place. Treatment with dextrose gel is inexpensive and simple to administer. Dextrose gel should be considered for first-line treatment to manage hypoglycaemia in late preterm and term babies in the first 48 h after birth. Waikato Medical Research Foundation, the Auckland Medical Research Foundation, the Maurice and Phyllis Paykel

Effectiveness of Topical Sucralfate in the Management of Pressure Ulcer in Hospitalized Patients: A Prospective, Randomized, Placebo-Controlled Trial.

Science.gov (United States)

Ala, Shahram; Saeedi, Majid; Gholipour, Afshin; Ahmadi, Motahareh; Asoodeh, Ali; Shiva, Afshin

2018-04-10

The aim of this study was to evaluate the effectiveness of topical sucralfate in the management of pressure ulcer (PU) in hospitalized patients. Forty hospitalized patients with stage II PU were included in this prospective, double-blind, randomized, placebo-controlled trial and were randomly divided into 2 groups receiving either sucralfate gel or placebo, on a daily basis. The patients were visited every day for 14 days, the ulcer was evaluated using the Pressure Ulcer Scale for Healing (PUSH) and changes to the measured scores over time were used as an indicator of wound healing. There were no statistically significant differences in any of the demographic characteristics between both groups. Both of the interventions reduced the average PUSH score, and at the end of the trial, all but 2 patients were healed. One in each group discontinued the trial because of exacerbation of the ulcer. No significant between-group difference in the average PUSH score reduction was observed (6.36 ± 2.11 vs. 5.89 ± 1.41, P = 0.42). Although the average healing time was less in the sucralfate group (6.05 ± 2.17 vs. 7.78 ± 3.42), the difference was not statistically significant (P = 0.07). Sucralfate gel does not improve healing of PU compared with placebo.

A double-blind placebo-controlled trial of omeprazole on urinary pH in healthy subjects

DEFF Research Database (Denmark)

Osther, P J; Rasmussen, L; Pedersen, S A

1992-01-01

Urinary pH is related to urinary calculus formation as well as urinary infection. Omeprazole is an effective inhibitor of gastric acid secretion through inhibition of the parietal cell H+K+ATPase. In this study we have evaluated a possible effect of omeprazole on urine acidification. Ten healthy...... male subjects took placebo and omeprazole, 40 mg o.m., for 10 days in a double-blind placebo-controlled trial. Morning fasting urinary pH was measured on day 10 of each treatment course using a pH meter. No effect of omeprazole on urinary pH could be demonstrated. It is thus unlikely...... that it is necessary to take omeprazole treatment into consideration in stone screening. As omeprazole did not affect urinary pH, no urological side effects related to changes in urinary pH can be expected....

Randomized, Placebo-Controlled Phase 2 Trial of a Lactobacillus crispatus Probiotic Given Intravaginally for Prevention of Recurrent Urinary Tract Infection

OpenAIRE

Stapleton, Ann E.; Au-Yeung, Melissa; Hooton, Thomas M.; Fredricks, David N.; Roberts, Pacita L.; Czaja, Christopher A.; Yarova-Yarovaya, Yuliya; Fiedler, Tina; Cox, Marsha; Stamm, Walter E.

2011-01-01

In a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (LACTIN-VÜ, Osel, Inc.) for prevention of recurrent UTI (rUTI) in pre-menopausal women, LACTIN-V was safe, well tolerated, and associated with a reduction in rUTI.

Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo-controlled, double-blind, randomized trial.

Science.gov (United States)

Harada, Tasuku; Momoeda, Mikio

2016-12-01

To evaluate the efficacy and safety of an ultra-low-dose oral contraceptive (NPC-01; 0.02 mg ethinyl estradiol and 1 mg norethisterone) in subjects with dysmenorrhea. Placebo-controlled, double-blind, randomized trial. Clinical trial sites. Two hundred fifteen subjects with dysmenorrhea. Subjects were randomly assigned to receive NPC-01, placebo, or IKH-01 (0.035 mg ethinyl estradiol and 1 mg norethisterone) for four cycles. Total dysmenorrhea score (verbal rating scale) assessing pain on the basis of limited ability to work and need for analgesics. The reductions of total dysmenorrhea score and visual analog scale score after the treatment were significantly higher in the NPC-01 group than in the placebo group. Furthermore, the efficacy of NPC-01 was comparable to that of IKH-01. The overall incidence of side effects was significantly higher in the NPC-01 group than in the placebo group. All side effects that occurred in the NPC-01 group were previously reported in patients receiving IKH-01. No serious side effects occurred. The ultra-low-dose contraceptive NPC-01 relieved dysmenorrhea as effectively as IKH-01. Thus, NPC-01 could represent a new option for long-term treatment of dysmenorrhea. NCT01129102. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference.

Science.gov (United States)

Black, Jed; Pillar, Giora; Hedner, Jan; Polo, Olli; Berkani, Ouali; Mangialaio, Sara; Hmissi, Abdel; Zammit, Gary; Hajak, Goran

2017-08-01

The orally active dual OX 1 R and OX 2 R antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults. Prospective, randomized, double-blind, placebo-controlled, active referenced trial in male and female adults aged 18-64 years with chronic, primary insomnia. Patients were randomized 1:1:1:1 to receive placebo, almorexant 100 mg, almorexant 200 mg, or zolpidem 10 mg (active reference) for 16 days. Primary efficacy assessments were objective (polysomnography-measured) and subjective (patient-recorded) wake time after sleep onset (WASO). Further sleep variables were also evaluated. From 709 randomized patients, 707 (mean age 45.4 years; 61.7% female) received treatment and 663 (93.8%) completed the study. A significant decrease versus placebo in median objective WASO was observed with almorexant 200 mg at the start and end of randomized treatment (-26.8 min and -19.5 min, respectively; both p system in insomnia disorder. CLINICALTRIALS. NCT00608985. Copyright © 2017 Elsevier B.V. All rights reserved.

Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

Vranken, J. H.; Hollmann, M. W.; van der Vegt, M. H.; Kruis, M. R.; Heesen, M.; Vos, K.; Pijl, A. J.; Dijkgraaf, M. G. W.

2011-01-01

The mechanisms underlying central neuropathic pain are poorly understood. Pain inhibitory mechanisms including sertononergic and norepinephrine systems may be dysfunctional. In this randomized, double-blinded, placebo-controlled trial we evaluated the effects of duloxetine on pain relief

Moderators of smoking cessation outcomes in a randomized-controlled trial of varenicline versus placebo.

Science.gov (United States)

Littlewood, Rae A; Claus, Eric D; Wilcox, Claire E; Mickey, Jessica; Arenella, Pamela B; Bryan, Angela D; Hutchison, Kent E

2017-12-01

Varenicline has gained a reputation as the optimal intervention for treatment resistant smokers, yet more than half of those who try it do not succeed. To better understand individual differences in the effectiveness of varenicline, this study evaluates the effectiveness of varenicline for smoking cessation in a double-blind, placebo-controlled, randomized clinical trial and examines the influence of psychological factors on treatment outcome. Two hundred five cigarette smokers interested in quitting were randomly assigned to 12 weeks of varenicline or placebo. Outcomes examined were CO-confirmed continuous abstinence for the past month, average number of cigarettes smoked per day, and 7-day point prevalence. Varenicline-treated participants were more likely than placebo to achieve continuous abstinence at the end of treatment (OR = 3.29; RR = 2.62), and 7-day point prevalence rates showed an effect of medication at each time point. Participants in both groups significantly reduced their smoking during the course of treatment and follow-up, and the medication by visit interaction was significant in the expected direction. Impulsivity and personality style emerged as moderators of the relationship between medication condition and treatment outcome. In addition to replicating efficacy results for varenicline versus placebo, the present study shows that the efficacy of pharmacotherapy is influenced by psychological factors. In an era where pharmacotherapy is often perceived as the "silver bullet," we are reminded that smoking cessation is a dynamic process and intervention must be adaptable to address individual differences.

Self-Administered Computer Therapy for Apraxia of Speech: Two-Period Randomized Control Trial With Crossover.

Science.gov (United States)

Varley, Rosemary; Cowell, Patricia E; Dyson, Lucy; Inglis, Lesley; Roper, Abigail; Whiteside, Sandra P

2016-03-01

There is currently little evidence on effective interventions for poststroke apraxia of speech. We report outcomes of a trial of self-administered computer therapy for apraxia of speech. Effects of speech intervention on naming and repetition of treated and untreated words were compared with those of a visuospatial sham program. The study used a parallel-group, 2-period, crossover design, with participants receiving 2 interventions. Fifty participants with chronic and stable apraxia of speech were randomly allocated to 1 of 2 order conditions: speech-first condition versus sham-first condition. Period 1 design was equivalent to a randomized controlled trial. We report results for this period and profile the effect of the period 2 crossover. Period 1 results revealed significant improvement in naming and repetition only in the speech-first group. The sham-first group displayed improvement in speech production after speech intervention in period 2. Significant improvement of treated words was found in both naming and repetition, with little generalization to structurally similar and dissimilar untreated words. Speech gains were largely maintained after withdrawal of intervention. There was a significant relationship between treatment dose and response. However, average self-administered dose was modest for both groups. Future software design would benefit from incorporation of social and gaming components to boost motivation. Single-word production can be improved in chronic apraxia of speech with behavioral intervention. Self-administered computerized therapy is a promising method for delivering high-intensity speech/language rehabilitation. URL: http://orcid.org/0000-0002-1278-0601. Unique identifier: ISRCTN88245643. © 2016 American Heart Association, Inc.

Randomized clinical trial of transversus abdominis plane block versus placebo control in live-donor nephrectomy.

Science.gov (United States)

Hosgood, Sarah A; Thiyagarajan, Umasanker M; Nicholson, Harriet F L; Jeyapalan, Inthira; Nicholson, Michael L

2012-09-15

Laparoscopic surgery reduces pain after donor nephrectomy; however, most patients still require a significant amount of postoperative parenteral opiate analgesia. Therefore, there is a need to investigate techniques that might further reduce postoperative pain. This study assessed the safety and efficacy of using a transversus abdominis plane (TAP) block in a randomized, double-blind, placebo-controlled trial. Forty-six patients were analyzed in the trial and were randomized to undergo the TAP block procedure with either bupivacaine (n=24) or saline placebo (Control n=22) injected into the muscle plane. Prefilled syringes were dispensed with the group allocation concealed to maintain blinding. After surgery, the amount of morphine, level of pain, and measures of recovery were recorded. The amount of morphine used 6 hr after surgery was significantly lower in patients receiving TAP block with bupivacaine compared with the control (presented as mean [SD], 12.4 [8.4] vs. 21.2 [14.0] mg; P=0.015). However, the total amount of morphine used was similar in both groups 45.6 [31.4] vs. 52.7 [28.8] mg; P=0.771. Patients in the bupivacaine group experienced significantly less pain on postoperative days 1 (score, 19 [15] vs. 37 [20]; P=0.003) and 2 (score, 11 [10] vs. 19 [13]; P=0.031). Recovery and postoperative hospital stay were similar in both groups. There were no complications associated with the procedure. The TAP block procedure is beneficial in reducing postoperative pain and early morphine requirements in laparoscopic live-donor nephrectomy.

Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Whitehorn, James; Nguyen, Chau Van Vinh; Khanh, Lam Phung; Kien, Duong Thi Hue; Quyen, Nguyen Than Ha; Tran, Nguyen Thi Thanh; Hang, Nguyen Thuy; Truong, Nguyen Thanh; Hue Tai, Luong Thi; Cam Huong, Nguyen Thi; Nhon, Vo Thanh; Van Tram, Ta; Farrar, Jeremy; Wolbers, Marcel; Simmons, Cameron P; Wills, Bridget

2016-02-15

Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy. Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms. Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures. We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe.Chinese Clinical Trials Registration. ISRCTN03147572. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

An evaluation of the cognitive and mood effects of an energy shot over a 6h period in volunteers: a randomized, double-blind, placebo controlled, cross-over study.

Science.gov (United States)

Wesnes, Keith A; Barrett, Marilyn L; Udani, Jay K

2013-08-01

Energy drinks are widely available mostly containing glucose, and several have been demonstrated to improve alertness and cognitive function; these effects generally being identified 30-60min after administration. The present study assessed whether an energy shot without carbohydrates would affect major aspects of cognitive function and also mood in volunteers over a 6h time period. This randomized, double-blind, placebo-controlled,crossover study compared the acute effects of the energy shot with a matching placebo in 94 healthy volunteers. Cognitive function was assessed with a widely used set of automated tests of attention and memory. Mood was assessed with the Bond-Lader, Beck Anxiety Index, Beck Depression Index, Chalder Fatigue Scales (CFS), and the POMS. The volunteers were requested to limit their sleep to between 3 and 6h the night before each testing day. Compared to the placebo, the energy shot significantly improved 6 validated composite cognitive function measures from the CDR System as well as self-rated alertness; the benefits on 4 of the cognitive measures still remaining at 6h. The overall effect sizes of the performance improvements were in the small to medium range and thus notable in this field. In conclusion, an energy shot can significantly improve important aspects of cognitive function for up to 6h compared to placebo in partially sleep-deprived healthy volunteers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Green tea polyphenols and Tai Chi for bone health: Designing a placebo-controlled randomized trial

Directory of Open Access Journals (Sweden)

Chyu Ming-Chien

2009-09-01

model of repeated measurements with random effect error terms was applied. Traditional procedures such as ANCOVA, chi-squared analysis, and regression were used for comparisons. Discussion We present the rationale, design, and methodology of a placebo-controlled randomized trial to investigate a new complementary and alternative medicine strategy featuring a dietary supplement and a mind-body exercise for alleviating bone loss in osteopenic postmenopausal women. Trial registration ClinicalTrials.gov identifier: NCT00625391

Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

Directory of Open Access Journals (Sweden)

Forbes Andrew

2010-10-01

Full Text Available Abstract Background Hip osteoarthritis (OA is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function. Methods The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline. Conclusions The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044

Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

Science.gov (United States)

2010-01-01

Background Hip osteoarthritis (OA) is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function. Methods The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS) and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline. Conclusions The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044 PMID:20946621

Should we reconsider the routine use of placebo controls in clinical research?

Directory of Open Access Journals (Sweden)

Avins Andrew L

2012-04-01

Full Text Available Abstract Background Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. Methods We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. Results We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Conclusions Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

Should we reconsider the routine use of placebo controls in clinical research?

Science.gov (United States)

Avins, Andrew L; Cherkin, Daniel C; Sherman, Karen J; Goldberg, Harley; Pressman, Alice

2012-04-27

Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

EFFICACY OF CITALOPRAM IN TREATMENT OF PATHOLOGICAL SKIN PICKING, A RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL

Directory of Open Access Journals (Sweden)

M Arbabi

2008-11-01

Full Text Available "nVarious studies suggest that selective serotonin reuptake inhibitors (SSRIs may be useful in treating pathological skin picking (PSP. This study sought to assess effectiveness of citalopram in comparison with placebo in treating PSP. Forty five individuals with PSP were recruited in a four-week, randomized clinical trial of citalopram (20 mg/day in comparison with placebo. Study measures assessing skin picking severity, mental health status, obsessive compulsive disorder and quality of life were given at baseline, weeks 2 and 4. PSP severity, general health status, obsession-compulsion severity and quality of life level were similar between two groups at baseline (P > 0.05. Treatment analyses revealed significant improvements in quality of life, general health status and obsession-compulsion severity in citalopram group compared to placebo group (P < 0.05. Mean PSP severity reduction in citalopram group was more than placebo group but this difference was not significant. Citalopram can improve general health status and quality of life in individuals with PSP but its effect on skin picking behavior doesn't differ significantly with placebo. Other trials with longer time are needed to determine the exact efficacy of citalopram on PSP

Zinc Sulfate: An Effective Micronutrient for Common Colds in Children: A Double-Blind Placebo Controlled Trial

Directory of Open Access Journals (Sweden)

Mehdi Gholamzadeh Baeis

2017-10-01

Full Text Available Background Cold is defined as a viral infection of the upper respiratory tract. The disease is more common in children than in adults and usually requires greater attention and care. Methods This double-blind randomized placebo-controlled trial (zinc versus placebo of zinc was carried out using a repeated measures design. After excluding the cases that met the exclusion criteria, data was collected from 120 participants and analyzed. The study was conducted over a period of 3 months (June 2015 to August 2015. The intervention group received Zinc (1 mg/kg for 7 days and the control group received the same amount of placebo. Results The durations of runny nose and nasal congestion was significantly shorter in patients in the intervention group, who had received zinc, when compared with the control group (P = 0.017 and P = 0.001, respectively. Moreover, there were significant differences between patients, who received zinc and those, who did not receive the drug, in terms of the duration, severity of signs and symptoms, severity of illness, and weakness (P = 0.018. Conclusions Based on the results of this study and other similar studies, zinc sulfate has positive effects on children with colds. Thus, the results of these studies could be utilized by medical teams to adopt a more accurate and complete clinical approach towards the use of zinc sulfate for patients with colds.

Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Li, Jin; Qin, Shukui; Xu, Ruihua; Yau, Thomas C C; Ma, Brigette; Pan, Hongming; Xu, Jianming; Bai, Yuxian; Chi, Yihebali; Wang, Liwei; Yeh, Kun-Huei; Bi, Feng; Cheng, Ying; Le, Anh Tuan; Lin, Jen-Kou; Liu, Tianshu; Ma, Dong; Kappeler, Christian; Kalmus, Joachim; Kim, Tae Won

2015-06-01

In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without other uncontrolled medical disorders. We randomly allocated patients (2:1; with a computer-generated unicentric randomisation list [prepared by the study funder] and interactive voice response system; block size of six; stratified by metastatic site [single vs multiple organs] and time from diagnosis of metastatic disease [regorafenib 160 mg once daily or placebo on days 1-21 of each 28 day cycle; patients in both groups were also to receive best supportive care. Participants, investigators, and the study funder were masked to treatment assignment. The primary endpoint was overall survival, and we analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01584830. Between April 29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204 patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a median follow-up of 7·4 months (IQR 4·3-12·2), overall survival was significantly better with regorafenib

Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial

Directory of Open Access Journals (Sweden)

Lanza FL

2018-04-01

Full Text Available Frank L Lanza,1 Agron Collaku,2 Dongzhou J Liu3 1Department of Gastroenterology, Houston Institute for Clinical Research, Houston, TX, USA; 2Biostatistics Department, GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA; 3Global Clinical Development, GlaxoSmithKline, Collegeville, PA, USA Background: While gastrointestinal (GI effects of standard ibuprofen and N-acetyl-p-­aminophenol (APAP have been reported, upper GI injury following treatment with fast-dissolving (FD formulations of these analgesics has not been investigated. We evaluated upper GI effects of over-the-counter doses of 2 FD ibuprofen products and 1 FD-APAP product. Methods: In a randomized, placebo-controlled, endoscopist-blinded, 4-way crossover study, 28 healthy subjects received FD ibuprofen 2×200 mg liquid capsules 3 times daily (TID, ibuprofen 2×200 mg tablets TID, FD-APAP 2×500 mg tablets 4 times daily (QID, and placebo 2×500 mg tablets QID for 7 days. The primary end point was gastric mucosal damage assessed by endoscopy using the Lanza scale: 0=normal stomach or proximal duodenum, 1=mucosal hemorrhages only, 2=1 or 2 erosions, 3=numerous (3–10 erosions, and 4=large number of erosions (>10 or ulcer. Secondary end points included duodenal mucosal damage (Lanza scale; gastroduodenal mucosal injury, classified as present (gastric and/or duodenal endoscopy score ≥2 or absent (gastric and/or duodenal endoscopy score <2; and number of hemorrhages, erosions, and ulcers counted separately in the stomach and duodenum. Results: Significantly greater gastric mucosal injury was observed after treatment with both ibuprofen products vs FD-APAP (p<0.0001 and p=0.0095, respectively. FD-APAP showed no difference from placebo (p=0.4794. The odds of having an incidence of gastroduodenal mucosal injury were over 6 times greater from FD ibuprofen liquid capsule treatment (odds ratio [OR]=6.19, 95% confidence interval [CI]: 1.60, 23.97 and over 3 times greater from ibuprofen

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

Science.gov (United States)

Robb, Adelaide; Bose, Anjana

2013-01-01

Abstract Objective The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods Adolescents (12–17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10–20 mg versus placebo could enroll in a 16–24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were

Can homeopathically prepared mercury cause symptoms in healthy volunteers? A randomized, double-blind placebo-controlled trial.

Science.gov (United States)

Vickers, A J; van Haselen, R; Heger, M

2001-04-01

To pilot a method for determining whether homeopathically prepared mercury causes more symptoms (a "drug proving") in healthy volunteers than placebo. One hundred and eighteen (118) healthy volunteers ages 18 to 65 were recruited by local advertising. Subjects unfamiliar with homeopathy undertook a 1-week single-blind placebo run-in, a 1-week of double-blind, randomized treatment on either homeopathically prepared mercury 12C or placebo, and a third week of placebo run-out. Each day, symptoms were recorded on a checklist that included both true mercury symptoms and symptoms not expected to be caused by mercury (false symptoms). Additional symptoms were assessed by open reporting. Outcome was assessed by calculating a score for each day as the number of true symptoms minus the number of false symptoms. The mean score during placebo was then subtracted from the mean score for weeks two and three of the trial. Fourteen (14) subjects dropped out during placebo run-in. The remaining 104 completed the trial. Baseline comparability was good. Mean difference score was -0.125 (SD 3.47) for mercury and -0.221 (SD 3.01) for placebo (p > 0.2). No significant differences between groups were found for the number of subjects meeting predefined criteria for a drug-proving reaction. This pilot study failed to find evidence that mercury 12C causes significantly more symptoms in healthy volunteers than placebo. Questionnaires with a limited number of gross symptoms do not seem to be an appropriate methodological technique in drug proving research. If drug-proving phenomena exist, they appear to be rare.

Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer

International Nuclear Information System (INIS)

Brose, Marcia S; Schlumberger, Martin; Nutting, Christopher M; Sherman, Steven I; Shong, Young Kee; Smit, Johannes WA; Reike, Gerhard; Chung, John; Kalmus, Joachim; Kappeler, Christian

2011-01-01

The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC. DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI-refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles), whereas safety will be evaluated every 28 days (1 cycle) for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS); patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate, response rate, duration of response, safety, and

A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): an Alliance trial.

Science.gov (United States)

Jatoi, A; Steen, P D; Atherton, P J; Moore, D F; Rowland, K M; Le-Lindqwister, N A; Adonizio, C S; Jaslowski, A J; Sloan, J; Loprinzi, C

2017-08-01

Multiple pilot studies, including one in colorectal cancer patients, suggest that creatine, an amino acid derivative, augments muscle, improves strength, and thereby could palliate the cancer anorexia/weight loss syndrome. In this randomized, double-blind, placebo-controlled trial, incurable patients with this syndrome were assigned creatine (20 g/day load×5 days followed by 2 g/day orally) versus identical placebo. Patients were weighed once a week for 1 month and then monthly. Patients were also assessed over 1 month for appetite and quality of life (validated questionnaires), fist grip strength, body composition (bioelectrical impedance), and adverse events. The primary endpoint was 10% or greater weight gain from baseline during the first month. Within this combined cohort of 263 evaluable patients (134 received creatine and 129 placebo), only 3 gained ≥10% of their baseline weight by 1 month: two creatine-treated and the other placebo-exposed (P = 1.00). Questionnaire data on appetite, quality of life, and activities of daily living showed no statistically significant differences between groups. Similarly, no statistically significant differences between groups were observed for fist-grip strength or body composition. Rates and severity of adverse events were comparable between groups. Finally, a median survival of 230 and 239 days were observed in the creatine and placebo groups, respectively (P = 0.70). Creatine, as prescribed in this trial, had no effect on the cancer anorexia/weight loss syndrome. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

N-Acetylcysteine in the Treatment of Pediatric Tourette Syndrome: Randomized, Double-Blind, Placebo-Controlled Add-On Trial.

Science.gov (United States)

Bloch, Michael H; Panza, Kaitlyn E; Yaffa, Alisa; Alvarenga, Pedro G; Jakubovski, Ewgeni; Mulqueen, Jilian M; Landeros-Weisenberger, Angeli; Leckman, James F

2016-05-01

Current pharmacological treatments for Tourette Syndrome (TS), such as antipsychotic agents and α-2 agonists, are moderately effective in the treatment of tics, but have substantial side effects that limit their use. N-acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as an antioxidant agent with minimal side effects for decades. NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders. We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind, placebo-controlled, add-on study. Thirty-one children and adolescents 8-17 years of age with TS were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total tic score. Secondary measures assessed comorbid obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD). Linear mixed models in SAS were used to examine differences between NAC and placebo. Of 31 randomized subjects, 14 were assigned to placebo (two females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years) treatment. No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes. We found no evidence for efficacy of NAC in treating tic symptoms. Our findings stand in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults, including OCD and trichotillomania, but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC.

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial

NARCIS (Netherlands)

Martinez de Tejada, B.; Karolinski, A.; Ocampo, M. C.; Laterra, C.; Hösli, I.; Fernández, D.; Surbek, D.; Huespe, M.; Drack, G.; Bunader, A.; Rouillier, S.; López de Degani, G.; Seidenstein, E.; Prentl, E.; Antón, J.; Krähenmann, F.; Nowacki, D.; Poncelas, M.; Nassif, J. C.; Papera, R.; Tuma, C.; Espoile, R.; Tiberio, O.; Breccia, G.; Messina, A.; Peker, B.; Schinner, E.; Mol, B. W.; Kanterewicz, L.; Wainer, V.; Boulvain, M.; Othenin-Girard, V.; Bertolino, M. V.; Irion, O.; Tellenbach, M.; Vögele, E.; Azbar, R.; Raggi, A.; Birkenmaier, A.; Kann, S.; Scheibner, K.; Huguelet, M.; Amann, E.; Baumann, M.; Jakob, E.; Biedermann, K.; Hodel, M.; Fischer, T.; Pfau, K.; Estermann, K.

2015-01-01

To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to

Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection.

Science.gov (United States)

Stapleton, Ann E; Au-Yeung, Melissa; Hooton, Thomas M; Fredricks, David N; Roberts, Pacita L; Czaja, Christopher A; Yarova-Yarovaya, Yuliya; Fiedler, Tina; Cox, Marsha; Stamm, Walter E

2011-05-01

Urinary tract infections (UTIs) are common among women and frequently recur. Depletion of vaginal lactobacilli is associated with UTI risk, which suggests that repletion may be beneficial. We conducted a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V; Osel) for prevention of recurrent UTI in premenopausal women. One hundred young women with a history of recurrent UTI received antimicrobials for acute UTI and then were randomized to receive either Lactin-V or placebo daily for 5 d, then once weekly for 10 weeks. Participants were followed up at 1 week and 10 weeks after intervention and for UTIs; urine samples for culture and vaginal swabs for real-time quantitative 16S ribosomal RNA gene polymerase chain reaction for L. crispatus were collected. Recurrent UTI occurred in 7/48 15% of women receiving Lactin-V compared with 13/48 27% of women receiving placebo (relative risk [RR], .5; 95% confidence interval, .2-1.2). High-level vaginal colonization with L. crispatus (≥10(6) 16S RNA gene copies per swab) throughout follow-up was associated with a significant reduction in recurrent UTI only for Lactin-V (RR for Lactin-V, .07; RR for placebo, 1.1; P < .01). Lactin-V after treatment for cystitis is associated with a reduction in recurrent UTI. Larger efficacy trials of this novel preventive method for recurrent UTI are warranted. CLINICAL TRIALS REGISTRATION. NCT00305227.

Fluoxetine for Maintenance of Remission and to Improve Quality of Life in Patients with Crohn's Disease: a Pilot Randomized Placebo-Controlled Trial.

Science.gov (United States)

Mikocka-Walus, Antonina; Hughes, Patrick A; Bampton, Peter; Gordon, Andrea; Campaniello, Melissa A; Mavrangelos, Chris; Stewart, Benjamin J; Esterman, Adrian; Andrews, Jane M

2017-04-01

Previous studies have shown that antidepressants reduce inflammation in animal models of colitis. The present trial aimed to examine whether fluoxetine added to standard therapy for Crohn's disease [CD] maintained remission, improved quality of life [QoL] and/or mental health in people with CD as compared to placebo. A parallel randomized double-blind placebo controlled trial was conducted. Participants with clinically established CD, with quiescent or only mild disease, were randomly assigned to receive either fluoxetine 20 mg daily or placebo, and followed for 12 months. Participants provided blood and stool samples and completed mental health and QoL questionnaires. Immune functions were assessed by stimulated cytokine secretion [CD3/CD28 stimulation] and flow cytometry for cell type. Linear mixed-effects models were used to compare groups. Of the 26 participants, 14 were randomized to receive fluoxetine and 12 to placebo. Overall, 14 [54%] participants were male. The mean age was 37.4 [SD=13.2] years. Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn's Disease Activity Index [F(3, 27.5)=0.064, p=0.978] or faecal calprotectin [F(3, 32.5)=1.08, p=0.371], but did have modest effects on immune function. There was no effect of fluoxetine on physical, psychological, social or environmental QoL, anxiety or depressive symptoms as compared to placebo [all p>0.05]. In this small pilot clinical trial, fluoxetine was not superior to placebo in maintaining remission or improving QoL. [ID: ACTRN12612001067864.]. © European Crohn’s and Colitis Organistion (ECCO) 2016.

Mast cell stabilizers as a potential treatment for Irritable bowel syndrome: A randomized placebo-controlled clinical trial

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N Ebrahimi Daryani

2009-08-01

Full Text Available Objectives: Mast cells are believed to play a role in irritable bowel syndrome pathogenesis and symptom genesis due to their close neighborhood to gastrointestinal innervations. This study was designed to evaluate the efficacy of orally administered cromolyn for reduction of symptoms in patients with irritable bowel syndrome (IBS. Material and Methods s: A randomized placebo-controlled double-blinded 6×6 weeks cross-over study was performed in a private gastrointestinal clinic. 10 patients were allocated to group A and 6 patients to group B. Patients in group A received 150 mg cromolyn divided in three equal doses for the first 6 weeks and placebo for the next 6 weeks but patients in group B received placebo for the first 6 weeks and cromolyn in the next 6 weeks. Weekly evaluation was performed and visual analogue scale was used to determine severity of symptoms. Results: Sixteen patients completed the study. Mean age of the patients was 40.3 ± 10.9 years old [range: 24-57]. Eight patients had D-IBS (Diarrhea dominant and other 8 had C-IBS (Constipation dominant. Both cromolyn sodium and the placebo decreased the severity of bloating (Freidman test, p 0.001 and 0.006 respectively. The severity of the main symptom (diarrhea or constipation did not decrease in patients of group A and B who were treated with different sequences of the drug or placebo. The severity of pain decreased drastically after 6th week of treatment with cromolyn. Freidman test showed a significant difference between the pain levels of the former defined treatment spots (p 0.01, and 0.02 for patients in group A and B, respectively. No adverse drug reactions were observed during the study. Conclusion: In conclusion, long term administration of cromolyn seems to be partially effective for treatment of abdominal pain in patients with IBS while main symptoms (diarrhea or constipation might not decrease during this treatment.

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

Science.gov (United States)

Mordi, Natalie A; Mordi, Ify R; Singh, Jagdeep S; Baig, Fatima; Choy, Anna-Maria; McCrimmon, Rory J; Struthers, Allan D; Lang, Chim C

2017-01-01

Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer

Predictors of placebo response in adults with attention-deficit/hyperactivity disorder: data from 2 randomized trials of osmotic-release oral system methylphenidate

NARCIS (Netherlands)

Buitelaar, J.K.; Sobanski, E.; Stieglitz, R.D.; Dejonckheere, J.; Waechter, S.; Schauble, B.

2012-01-01

OBJECTIVE: To find potential correlates of placebo response in adults with attention-deficit/hyperactivity disorder (ADHD) and gain insights into why placebo response may be high in clinical trials. METHOD: Post hoc analysis of placebo data from 2 randomized controlled trials of osmotic-release oral

The effect of vitamin-mineral supplementation on the intelligence of American schoolchildren: a randomized, double-blind placebo-controlled trial.

Science.gov (United States)

Schoenthaler, S J; Bier, I D; Young, K; Nichols, D; Jansenns, S

2000-02-01

Many medical, nutrition, and education professionals have long suspected that poor diet impairs the academic performance of Western schoolchildren; academic performance often improves after improved diet. However, others have suggested that such academic gains may be due to psychologic effects rather than nutrition. To resolve this issue, two independent research teams conducted randomized trials in which children were given placebos or low-dose vitamin-mineral tablets designed to raise nutrient intake to the equivalent of a well-balanced diet. Both teams reported significantly greater gains in nonverbal intelligence among the supplemented groups. The findings were important because of the apparent inadequacy of diet they revealed and the magnitude of the potential for increased intelligence. However, none of the ten subsequent replications, or the two original trials, were without limitations leaving this issue in controversy. To determine if schoolchildren who consume low-dose vitamin-mineral tablets will have a significantly larger increase in nonverbal intelligence than children who consume placebos in a study that overcomes the primary criticisms directed at the previous 12 controlled trials. A double-blind, placebo-controlled trial using stratified randomization within each teacher's class based on preintervention nonverbal intelligence. Two "working class," primarily Hispanic, elementary schools in Phoenix, Arizona, participated in the study. Slightly more than half the teachers in each school distributed the tablets daily to 245 schoolchildren aged 6 to 12 years. Daily vitamin-mineral supplementation at 50% of the U.S. daily recommended allowance (RDA) for 3 months versus placebo. Post-test nonverbal IQ, as measured by the Wechsler Intelligence Scale for Children-Revised (WISC-R), while controlling for pretest nonverbal IQ as a covariate. FOUR MAIN RESULTS: First, a significant difference of 2.5 IQ points (95% CI: 1.85-3.15) was found between 125 children

Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy as treatment of sudden sensorineural hearing loss.

Science.gov (United States)

Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M

2009-01-01

To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p < 0.05). Mean hearing gains, pure tone averages, speech reception thresholds and subjective recovery rates were significantly better in ozone-treated patients compared with placebo-treated patients (p < 0.05). Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.

Antiobesity Effect of Caraway Extract on Overweight and Obese Women: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial

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Mahnaz Kazemipoor

2013-01-01

Full Text Available Caraway (Carum carvi L., a potent medicinal plant, is traditionally used for treating obesity. This study investigates the weight-lowering effects of caraway extract (CE on physically active, overweight and obese women through a randomized, triple-blind, placebo-controlled clinical trial. Seventy overweight and obese, healthy, aerobic-trained, adult females were randomly assigned to two groups (n=35 per group. Participants received either 30 mL/day of CE or placebo without changing their diet or physical activity. Subjects were examined at baseline and after 90 days for changes in body composition, anthropometric indices, and clinical and paraclinical variables. The treatment group, compared with placebo, showed a significant reduction of weight, body mass index, body fat percentage, and waist-to-hip ratio. No changes were observed in lipid profile, urine-specific gravity, and blood pressure of subjects. The results suggest that a dietary CE with no restriction in food intake, when combined with exercise, is of value in the management of obesity in women wishing to lower their weight, BMI, body fat percentage, and body size, with no clinical side effects. In conclusion, results of this study suggest a possible phytotherapeutic approach for caraway extract in the management of obesity. This trial is registered with NCT01833377.

Safety and Efficacy of MLC601 in Iranian Patients after Stroke: A Double-Blind, Placebo-Controlled Clinical Trial

Directory of Open Access Journals (Sweden)

A. A. Harandi

2011-01-01

Full Text Available Objective. To investigate the safety and efficacy of MLC601 (NeuroAid as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 1 month ischemic stroke. All patients were given either MLC601 (100 patients or placebo (50 patients, 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P>.05. Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P<.001. Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases.

Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine.

Science.gov (United States)

Gibbons, Robert D; Hur, Kwan; Brown, C Hendricks; Davis, John M; Mann, J John

2012-06-01

Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression. To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations. Reanalysis of all intent-to-treat person-level longitudinal data during the first 6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Children's Depression Rating Scale-Revised scores (youth population), Hamilton Depression Rating Scale scores (adult and geriatric populations), and estimated response and remission rates at 6 weeks were analyzed for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving extended-release venlafaxine. Patients in all age and drug groups had significantly greater improvement relative to control patients receiving placebo. The differential rate of improvement was largest for adults receiving fluoxetine (34.6% greater than those receiving placebo). Youths had the largest treated vs control difference in response rates (24.1%) and remission rates (30.1%), with adult differences generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients had the smallest drug-placebo differences, an 18.5% greater rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced larger effects than extended-release venlafaxine. Baseline severity could not be shown to affect symptom reduction. To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that

Are all placebo effects equal? Placebo pills, sham acupuncture, cue conditioning and their association.

Directory of Open Access Journals (Sweden)

Jian Kong

Full Text Available Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol, sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for "placebo responders." However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

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Devanand, D P; Nobler, Mitchell S; Cheng, Jocelyn; Turret, Nancy; Pelton, Gregory H; Roose, Steven P; Sackeim, Harold A

2005-01-01

The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.

Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.

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Mary P McGowan

Full Text Available Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated.Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n  = 58 were ≥18 years with LDL-C ≥7.8 mmol/L or LDL-C ≥5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n  = 39 or placebo (n  = 19 were added to lipid-lowering therapy for 26 weeks.percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27 reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18 from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001. Mipomersen produced statistically significant (p<0.001 reductions in apolipoprotein B and lipoprotein(a, with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%, 39(100%; serious adverse events, 0(0%, 6(15.4%; discontinuations due to adverse events, 1(5.3%, 8(20.5% and cardiac adverse events, 1(5.3%, 5(12.8%.Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and lipoprotein(a. Mounting evidence suggests it may be a

Polyethylene glycol 3350 in occasional constipation: A one-week, randomized, placebo-controlled, double-blind trial.

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McGraw, Thomas

2016-05-06

To evaluate the efficacy and safety of polyethylene glycol (PEG) 3350 in subjects with self-reported occasional constipation. Eligible subjects ≥ 17 years of age were randomized to receive either placebo or PEG 3350 17 g once daily in this multicenter, double-blind trial. Evaluations were conducted before (baseline) and after a 7-d treatment period. The primary efficacy variable was the proportion of subjects reporting complete resolution of straining and hard or lumpy stools. Secondary efficacy variables assessed the severity of the subjects' daily bowel movement (BM) symptoms, and preference of laxatives based on diary entries, visual analog scale scores, and questionnaires. Of the 203 subjects enrolled in the study, 11 had major protocol violations. Complete resolution was noted by 36/98 (36.7%) subjects in the PEG 3350 group and 23/94 (24.5%) in the placebo group (P = 0.0595). The number of complete BMs without straining or lumpy stools was similar between both groups. Subjects receiving PEG 3350 experienced significant relief in straining and reduction in hardness of stools over a 7-d period (P PEG 3350 had a better effect on their daily lives, provided better control over a BM, better relief from constipation, cramping, and bloating, and was their preferred laxative. Adverse events (AEs) were balanced between the PEG 3350 and the placebo groups. No deaths, serious AEs, or discontinuations due to AEs were reported. This trial is registered at clinicaltrials.gov as NCT00770432. Oral administration of 17 g PEG 3350 once daily for a week is effective, safe, and well tolerated in subjects with occasional constipation.

Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

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Motokazu Kato

Full Text Available ABSTRACT: Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days. Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years, 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001. The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points. All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. KEY WORDS: beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome.

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David R Strayer

Full Text Available BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue. The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C(12U, in patients with debilitating CFS/ME. METHODS AND FINDINGS: A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET. Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS, Activities of Daily Living (ADL, and Vitality Score (SF 36. Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047 from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022. The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048. Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04. Rintatolimod at 400 mg twice weekly was generally well-tolerated. CONCLUSIONS/SIGNIFICANCE: Rintatolimod produced objective improvement in ET and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00215800.

Vitamin E in aging persons with Down syndrome: A randomized, placebo-controlled clinical trial.

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Sano, Mary; Aisen, Paul S; Andrews, Howard F; Tsai, Wei-Yann; Lai, Florence; Dalton, Arthur J

2016-05-31

To determine whether vitamin E would slow the progression of cognitive deterioration and dementia in aging persons with Down syndrome (DS). A randomized, double-blind controlled clinical trial was conducted at 21 clinical sites, and researchers trained in research procedures recruited adults with DS older than 50 years to participate. Participants were randomly assigned to receive 1,000 IU of vitamin E orally twice daily for 3 years or identical placebo. The primary outcome was change on the Brief Praxis Test (BPT). Secondary outcomes included incident dementia and measures of clinical global change, cognition, function, and behavior. A total of 337 individuals were randomized, 168 to vitamin E and 169 to placebo. Both groups demonstrated deterioration on the BPT with no difference between drug and placebo. At baseline, 26% were diagnosed with dementia and there was an overall rate of incident dementia of 11%/year with no difference between groups. There was no effect on the secondary outcome measures. Though numerically higher in the treatment group, there was no difference in the number of adverse events (p = 0.079) and deaths (p = 0.086) between groups. Vitamin E did not slow the progression of cognitive deterioration in older individuals with DS. This study provides Class II evidence that vitamin E does not significantly slow the progression of cognitive deterioration in aging persons with DS. © 2016 American Academy of Neurology.

Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

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Dannon, P N; Sasson, Y; Hirschmann, S; Iancu, I; Grunhaus, L J; Zohar, J

2000-05-01

To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

The efficacy of azithromycin in pityriasis rosea: A randomized, double-blind, placebo-controlled trial

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Deepika Pandhi

2014-01-01

Full Text Available Background: Macrolides are prescribed in the treatment of pityriasis rosea despite conflicting results of the limited number of studies evaluating their role in its treatment. Aim: A randomized double-blind placebo-controlled trial was conducted to evaluate the effect of azithromycin on the clinical course of pityriasis rosea. Methods: Seventy patients of pityriasis rosea were given either azithromycin (n = 35 or placebo (n = 35 and were followed-up at 2, 4 and 6 weeks. Pruritus was assessed in both groups using the visual analogue scale (VAS . Change in the pityriasis rosea severity score (PRSS and in the VAS were recorded as outcome measures and were compared statistically. Results: The decrease in PRSS from baseline through 2, 4 and 6 weeks within both treatment (P < 0.001 and placebo (P < 0.001 arms was found to be statistically significant; however, this change was not significantly different in the two groups (P = 0.179. Similarly, the decrease in VAS was found to be statistically significant within both groups (P < 0.001; however, the change was comparable between the two groups (P < 0.937. Analysis by Fisher′s exact test did not find a significant difference between the two groups for PRSS and VAS. Conclusion: Azithromycin is not effective in pityriasis rosea and the use of macrolides for this disease should not be encouraged in clinical practice.

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

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Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

2013-01-01

Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

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Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L

2013-11-01

Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Baseline characteristics of participants in the JUPITER trial, a randomized placebo-controlled primary prevention trial of statin therapy among individuals with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein

NARCIS (Netherlands)

Ridker, Paul M.; Fonseca, Francisco A. H.; Genest, Jacques; Gotto, Antonio M.; Kastelein, John J. P.; Khurmi, Nardev S.; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J.; Nordestgaard, Borge G.; Shepherd, James; Willerson, James T.; Glynn, Robert J.

2007-01-01

The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a randomized, double-blind, placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein (LDL) cholesterol

Effect of almond consumption on vascular function in patients with coronary artery disease: a randomized, controlled, cross-over trial.

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Chen, C-Y Oliver; Holbrook, Monika; Duess, Mai-Ann; Dohadwala, Mustali M; Hamburg, Naomi M; Asztalos, Bela F; Milbury, Paul E; Blumberg, Jeffrey B; Vita, Joseph A

2015-06-17

Almonds reduce cardiovascular disease risk via cholesterol reduction, anti-inflammation, glucoregulation, and antioxidation. The objective of this randomized, controlled, cross-over trial was to determine whether the addition of 85 g almonds daily to a National Cholesterol Education Program (NCEP) Step 1 diet (ALM) for 6 weeks would improve vascular function and inflammation in patients with coronary artery disease (CAD). A randomized, controlled, crossover trial was conducted in Boston, MA to test whether as compared to a control NCEP Step 1 diet absent nuts (CON), incorporation of almonds (85 g/day) into the CON diet (ALM) would improve vascular function and inflammation. The study duration was 22 weeks including a 6-weeks run-in period, two 6-weeks intervention phases, and a 4-weeks washout period between the intervention phases. A total of 45 CAD patients (27 F/18 M, 45-77 y, BMI = 20-41 kg/m(2)) completed the study. Drug therapies used by patients were stable throughout the duration of the trial. The addition of almonds to the CON diet increased plasma α-tocopherol status by a mean of 5.8%, reflecting patient compliance (P ≤0.05). However, the ALM diet did not alter vascular function assessed by measures of flow-mediated dilation, peripheral arterial tonometry, and pulse wave velocity. Further, the ALM diet did not significantly modify the serum lipid profile, blood pressure, C-reactive protein, tumor necrosis factor-α or E-selectin. The ALM diet tended to decrease vascular cell adhesion molecule-1 by 5.3% (P = 0.064) and increase urinary nitric oxide by 17.5% (P = 0.112). The ALM intervention improved the overall quality of the diet by increasing calcium, magnesium, choline, and fiber intakes above the Estimated Average Requirement (EAR) or Recommended Dietary Allowance (RDA). Thus, the addition of almonds to a NECP Step 1 diet did not significantly impact vascular function, lipid profile or systematic inflammation in CAD patients receiving

Designing a placebo device: involving service users in clinical trial design.

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Gooberman-Hill, Rachael; Jinks, Clare; Bouças, Sofia Barbosa; Hislop, Kelly; Dziedzic, Krysia S; Rhodes, Carol; Burston, Amanda; Adams, Jo

2013-12-01

Service users are increasingly involved in the design of clinical trials and in product and device development. Service user involvement in placebo development is crucial to a credible and acceptable placebo for clinical trials, but such involvement has not yet been reported. To enhance the design of a future clinical trial of hand splints for thumb-base osteoarthritis (OA), service users were involved in splint selection and design of a placebo splint. This article describes and reflects on this process. Two fora of service users were convened in 2011. Service users who had been prescribed a thumb splint for thumb-base OA were approached about involvement by Occupational Therapy (OT) practitioners. A total of eight service users took part in the fora. Service users discussed their experience of OA and their own splints and then tried a variety of alternative splints. Through this they identified the active features of splints alongside acceptable and unacceptable design features. Service users focused on wearability and support with or without immobilization. Fora discussed whether a placebo group ('arm') was an acceptable feature of a future trial, and service users developed a potential design for a placebo splint. This is the first project that to involve service users in placebo design. Service users are increasingly involved in product and device design and are ideally placed to identify features to make a placebo credible yet lacking key active ingredients. The future trial will include research into its acceptability. © 2013 John Wiley & Sons Ltd.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial.

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Morice, Alyn H; McGarvey, Lorcan; Pavord, Ian D; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S

2017-07-01

To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. ClinicalTrials.gov: NCT01656668.

The Impact of Methylphenidate on Motor Performance in Children with both Attention Deficit Hyperactivity Disorder and Developmental Coordination Disorder: A Randomized Double-Blind Crossover Clinical Trial

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Robabeh Soleimani

2017-07-01

Full Text Available Background: Children with attention deficit hyperactivity disorder/developmental coordination disorder (ADHD/DCD suffer from problems associated with gross and fine motor skills. There is no effective pharmacological therapy for such patients. We aimed to assess the impact of methylphenidate (MPH on motor performance of children with ADHD/DCD. Methods: In this double-blind placebo-controlled, 17 children (12 boys with ADHD/DCD with a mean age of 7 years 6 months were recruited in Shafa Hospital, Rasht, Iran. The response was defined as ≥25% reduction in the total score of ADHD rating scale-IV from the baseline. Sixteen boys entered phase 2 of the study in which the impact of MPH on motor function was determined through a crossover randomized clinical trial. Eligible individuals were scheduled for baseline and two assessment visits after a one-week period of intervention. We used the short form of Bruininks-Oseretsky test (BOT-2 to identify the disability of motor function. Children were randomly assigned to receive MPH or inert ingredients (placebo. In the second period, medication (MPH/placebo was crossed over. The effects of MPH were analyzed using χ2 test for related samples to compare the performance during baseline, placebo, and MPH trials. The results were analyzed using the SPSS software version 16.0. Results: The mean minimal effective dose of MPH per day was 17.3 mg (0.85 mg/kg. Children with higher ADHD rating scale had a significantly lower standard score in BOT-2 (P=0.03. Following MPH intake, 26.6% of the children showed clinically significant improvement in motor function. However, the improvement was not statistically different between the MPH and placebo. Conclusion: Although MPH improved ADHD symptoms, problems with motor performance still remained. Further work is required to determine the probable effects of MPH in a higher dosage or in different subtypes of ADHD. Trial Registration Number: IRCT201107071483N2

A randomized, double-blind, placebo-controlled trial of paracetamol and ketoprofren lysine salt for pain control in children with pharyngotonsillitis cared by family pediatricians

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Della Casa Alberighi Ornella